Archive for November, 2008

Chorea …The disease and the dance

November 27, 2008 at 12:46 am · Filed under Neurological section ·Tagged

The author: Professor Yasser Metwally

http://yassermetwally.com

INTRODUCTION

November 27 , 2008 — The term chorea comes from the Latin word “choreus,” which means dancing. Chorea has been defined by the ad hoc Committee on Classification of the World Federation of Neurology as “a state of excessive, spontaneous movements, irregularly timed, non-repetitive, randomly distributed and abrupt in character. These movements may vary in severity from restlessness with mild intermittent exaggeration of gesture and expression, fidgeting movements of the hands, unstable dance-like gait to a continuous flow of disabling, violent movements.”

Video 1. Chorea…the disease, a patient with Huntington chorea. In order to better appreciate the choreal movements look at the patients, choreal movement are unpredictable in time and place and the patient appears as if he or she is dancing. Compare the choreal movement in this patient with the dance in video 2,3 which is called chorea

Chorea involves proximal as well as distal muscles. In most patients, normal tone is noted but in some instances, hypotonia is present. In a busy movement disorder center, levodopa-induced chorea is the commonest movement disorder, followed by Huntington disease (HD).

Video 2. Chorea…The dance

Video 2. Chorea…The dance

References

  1. Metwally, MYM: Textbook of neuroimaging, A CD-ROM publication, (Metwally, MYM editor) WEB-CD agency for electronic publication, version 9.2a April 2008 [Click to have a look at the home page]

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Amyloid Deposits Found in More Than 20% of Cognitively Normal Seniors

November 27, 2008 at 12:25 am · Filed under Neurological section

The author: Professor Yasser Metwally

http://yassermetwally.com

INTRODUCTION

November 27 , 2008 — About 1 in 5 cognitively normal elderly people has signs of Alzheimer’s-related amyloid plaques in the brain, which is about the same proportion as found in brains of deceased patients who were diagnosed with Alzheimer’s disease (AD), a new study in the November issue of the Archives of Neurology has found.

In 1 of the first and largest studies of its kind, researchers used a novel amyloid-tracking agent called Pittsburgh Compound B (PiB) and positron-emission tomography (PET) to pick up areas of amyloid deposits in healthy living volunteers. In the past, it was only through autopsies that such plaque deposits could be detected.

“It’s very revolutionary that we can reliably detect the pathology of AD in living people,” said one of the investigators, Dr. William E. Klunk, MD, PhD, professor of psychiatry and neurology at the University of Pittsburgh School of Medicine, in Pennsylvania.

  • “Profound Implications”

These findings have “profound implications” for future preventive strategies and might lay the groundwork to possibly predict “fairly accurately” who will develop AD 5 to 10 years before the onset of symptoms, said the study authors.

“I see this as good news, bad news,” said Dr. Klunk . The good news is that scientists are at a point where they can now screen people and detect amyloid in time to intervene with therapy. The bad news is that there isn’t yet a proven therapy. “And as we sit here today, if we treat only people who have symptomatic Alzheimer’s disease, we’re already 10 years behind the pathology,” he said.

For the study, investigators included 43 healthy cognitively normal subjects between the ages of 65 and 88 years. “It’s important to note that this is a community-derived sample,” said Dr. Klunk. “They’re as representative of the typical elderly population as we could get.”

These subjects underwent a battery of neurological and cognitive assessments as well as the PET PiB scanning. PiB is a derivative of an older dye that detects amyloid but only in autopsy tissue, as it can’t enter the living brain. In a long and painstaking process, Dr. Klunk and his colleague Chester A. Mathis, PhD, professor of radiology at the University of Pittsburgh School of Medicine, modified that original compound to come up with an agent that not only can be used in a living brain but also is better at binding to amyloid.

  • Like Craft Glitter

Dr. Klunk likens the upgraded agent to craft glitter sprinkled over a paper dotted with glue. After turning the paper upside down, some of the glitter scatters but some sticks to the glue to create a pattern. “The paper is like the nonamyloid brain, the glue is like the amyloid in the brain, and the glitter is like PiB.”

To help define amyloid positivity, an additional 19 cognitively normal subjects underwent the same diagnostic neuropsychological screening and PiB PET scanning. Using a complicated system of eliminating outliers, investigators came up with a cutoff for amyloid-positive status.

The PET scans used in the study concentrated on particular regions of the brain, including: frontal lobe, anterior cingulate gyrus (ACG), lateral temporal, mesial temporal, occipital, parietal, precuneus cortex (PRC)/posterior cingulate gyrus (PCG), sensorimotor cortices, and anterior-ventral stratum.

  • Equal Cognitive Performance

Of the 43 cognitively normal subjects, 9 (21%) showed early amyloid deposits in at least 1 area of the brain — about the same percentage as is found in postmortem studies. Investigators found no differences in cognitive performance or in demographics between the amyloid-positive and amyloid-negative groups.

Significantly, the investigators also noted that the amyloid deposition was primary in regions that ultimately develop heavy amyloid loads in AD patients, especially the ACG and the PRC/PCG cortex

“These folks can tolerate the pathology, so there’s time to do something about it,” said Dr. Klunk. “They have amyloid, but the brain isn’t malfunctioning yet.”

Unexpectedly, the amyloid-positive group performed better on 1 of the cognitive tests — the delayed word-recall test — perhaps because they have particularly high cognitive reserves in areas such as the medial temporal lobe that are relatively unaffected by amyloid deposition. But Dr. Klunk does not want to place too much emphasis on this finding. “We did a lot of tests, so I don’t think the fact that 1 of them was a little better in the people who had amyloid than those who didn’t is the message,” he said. “What’s more important is that in all these tests, there’s really nothing to shake a stick at as far as picking the amyloid-positive people out from the amyloid-negative people.”

Will the 9 seniors with amyloid go on to develop AD, and are the other 34 subjects protected from developing this disease? “That’s what the research will tell us as we follow these people,” said Dr. Klunk. “But the working hypothesis for now is that the Alzheimer’s patients will come from this cohort who already has the pathology. We’ll find out if this is correct.”

  • “We’re Not There Yet”

Meanwhile, it would be ideal if these 9 patients could be treated to decrease the risk of developing AD. “We’re not there yet, although that’s obviously what we would love to do,” said Dr. Klunk, adding that he and his colleagues have some ideas of potential preventive approaches. One such approach could be to use 1 of the promising immunotherapies now being tested. “But we first need to show that the latest iteration of these immunotherapies is safe in AD patients and that they effectively remove amyloid from these patients,” he said.

Although he recognizes the value of autopsy studies, Dr. Klunk pointed out the advantages of PiB in detecting amyloid in the brain of cognitively normal people. For one thing, in the case of postmortem examinations in people with normal cognitive test results, the assessment may have taken place months or even years before death, raising the possibility that such individuals were not cognitively normal when they died.

“Also, if they were tested very close to death [and did not test normal], you can’t be sure if something related to their death affected their cognitive function, and, most important, you can’t follow them to then find out if this really was a precursor to AD or whether it was just an irrelevant finding in their brain.”

This research adds another element to the ongoing discussion of the relationship between amyloid and cognition. While some studies have found that the amyloid burden is related to the degree of cognitive impairment in AD, others have failed to uncover a correlation. This current study points to the complicated nature of this relationship, said Dr. Klunk. “It’s not a one-to-one thing,” he said. “Just as a certain mass of cholesterol in our arteries does not equal a certain number of heart attacks, a given mass of amyloid does not equal a given deficit on a cognitive test.”

References

  1. Arch Neurol. 2008;65:1509-1517. Abstract

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Subthalamic Nucleus Stimulation May Be Effective in Severe OCD, but Safety a Concern

November 27, 2008 at 12:20 am · Filed under Neurological section

The author: Professor Yasser Metwally

http://yassermetwally.com

INTRODUCTION

November 27, 2008 — Preliminary findings suggest that subthalamic nucleus stimulation may be effective in treating severe, refractory obsessive-compulsive disorder (OCD). However, the procedure is also associated with an increased risk for serious adverse events.

A 10-month crossover, double-blind, multicenter study assessing the efficacy and safety of the procedure showed that it significantly reduced symptom severity and improved global functioning in a group of patients with severe, highly refractory, primary OCD.

“We propose that the decrease in the obsessive-compulsive symptoms is due to changes in neuronal activity in the subthalamic nucleus, a theory that is consistent with the concept that the subthalamic nucleus is an integrative center for the motor, cognitive, and emotional components of behavior,” the authors, with principal investigator Luc Mallet, MD, from Pitié-Salpêtrière University Hospital, in Paris, France, write.

However, among 17 study subjects who had stimulators implanted, there were 15 serious adverse events experienced by 11 patients. Of these, 4 were related to the surgery and included 2 infections leading to implant removal, clumsiness and double vision with perielectrode edema, and 1 intracerebral hemorrhage, which resulted in a permanent finger palsy. There were also 23 nonserious adverse events.

The study is published in the November 13 issue of the New England Journal of Medicine.

  • Disabling Disorder

According to the study, approximately 25% to 40% of OCD patients do not respond to standard combination treatment with selective serotonin-reuptake inhibitors and cognitive behavioral therapy.

OCD “is one of the most disabling of the chronic psychiatric disorders and has considerable repercussions on family relationships, social life, and the ability to function at work,” the investigators write.

Ablative neurosurgical stereotactic treatments have also been explored for refractory OCD patients, with variable efficacy. In contrast, deep brain stimulation (DBS), which has been used since the late 1980s to effectively treat Parkinson’s disease (PD), offers the advantages of being adaptable and reversible.

It has also been reported that targeting the subthalamic nucleus with DBS can lead to substantial reductions in behavior disorders in PD patients, including repetitive behavior, anxiety, obsessive-compulsive symptoms, and OCD.

To test the safety and efficacy of the procedure in this patient population, investigators recruited 16 refractory OCD patients age 18 years and older who had a primary diagnosis of OCD with a duration of more than 5 years from 10 academic centers in France.

  • Primary Outcome

The randomized study included two 3-month phases separated by a 1-month washout period. One group of 8 subjects underwent active stimulation followed by a sham stimulation period, and the other group of 8 participants underwent sham stimulation followed by an active stimulation period.

A total of 18 patients were enrolled in the study between January 2005 and April 2006. One participant withdrew from the study, and the remaining 17 were implanted with stimulators. However, 1 patient had to have the stimulator removed before randomization due to an infection.

The study’s primary outcome was change in OCD symptom severity assessed by the Yale-Brown Obsessive Compulsive Scale (Y-BOCS) at the end of each period.

Any new symptom or worsening of an existing symptom was considered an adverse event. Adverse events were classified as serious if they required hospitalization, if they resulted in sequelae, or if the clinician deemed the event to be serious.

  • More Research Needed

According to the investigators the Y-BOCS score was significantly lower at the end of the active stimulation than at the end of the sham stimulation, independent of the group or study period.

In addition, scores on the Global Assessment Functioning (GAF) scale were significantly higher, indicating higher levels of functioning, following stimulation. Similarly, disease severity, measured by the Clinical Global Impression scale, was significantly improved with active stimulation.

At the end of the first phase of the study, 6 of the 8 patients (75%) in the active stimulation group had a response measured by the Y-BOCS score and 8 of 8 (100%) had a response as measured by the GAF scale.

In comparison, 3 of 8 subjects (38%) in the sham stimulation group had a response as measured by Y-BOCS and GAF scale.

While the findings are promising, the researchers note, “the occurrence of serious adverse events, the small number of patients, and the short duration of the study highlight the risks of stimulation of the subthalamic nucleus and the need for larger studies with longer follow-up.”

References

  1. N Engl J Med. 2008;359:2121-2134. Abstract

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PTSD Symptoms More Than Double Mortality Risk in Patients with ICDs

November 27, 2008 at 12:16 am · Filed under Neurological section

The author: Professor Yasser Metwally

http://yassermetwally.com

INTRODUCTION

November 27, 2008 — Individuals who receive implantable cardiac defibrillators (ICDs) after a sudden cardiac event are more than twice as likely to die within 5 years if they experience symptoms of posttraumatic stress disorder (PTSD), regardless of disease severity.

In a prospective cohort study, researchers from the Technische Universität Muenchen, in Munich, Germany, found that PTSD symptoms in this patient population were associated with a 2.4-fold increased mortality risk.

“We were struck by the finding that patients suffering from PTSD symptoms had a substantially higher risk of mortality, and it was particularly striking that this association was strengthened after adjustment for known risk factors. This study shows there is direct evidence that PTSD independently influences mortality risk,” said principal investigator Karl-Heinz Ladwig, MD, PhD.

The study was published in the November issue of Archives of General Psychiatry.

  • PTSD Generally Overlooked

According to Dr. Ladwig, PTSD is often overlooked in cardiac patients. Although it is generally recognized that ICD patients should undergo psychologic screening and possible treatment as part of their follow-up care, this does not always translate into clinical practice. “In part, this may have to do with the patients themselves, many of whom are resistant to this type of care and are intent on coping by themselves, but there is no doubt that they need help,” said Dr. Ladwig.

It is estimated that between 8% and 20% of patients with acute coronary syndromes and 27% to 38% of those who survive a cardiac arrest develop PTSD. The authors point out that a significant proportion of patients with an ICD have survived a cardiac arrest or an acute myocardial infarction, which can cause acute psychologic distress. Treatment with an ICD, although highly effective and lifesaving, could further contribute to psychologic distress by serving as a constant reminder of the underlying disease.

Recent research from the Veterans Affairs Normative Aging Study linked PTSD symptoms and coronary heart disease in a cohort of apparently healthy men. However, the researchers note, little is known about the effect of PTSD on patients with ICDs.

  • Impact on Prognosis

To determine the impact of PTSD on long-term mortality, investigators followed 211 patients with ICDs who routinely attended a cardiac outpatient clinic after a cardiac event in 1998. The study’s primary outcome was mortality risk per 1000 person-years.

Participants were surveyed an average of 27 months after implantation and, at that time, 38 reported severe PTSD symptoms and 109 reported low or moderate PTSD symptoms. During an average of 5.1 years, 45 (30.6%) of the patients died: 32 of 109 patients with low or moderate symptoms and 13 of 38 with high levels of symptoms.

In their adjusted analyses, which controlled for age, sex, diabetes mellitus, measures of cardiac disease, and comorbid anxiety and depression, the researchers found that PTSD symptoms substantially increased mortality risk.

Compared with 55 fatal events per 1000 person-years in patients without PTSD, the long-term absolute mortality risk accounted for 80 fatal events per 1000 person-years in patients with PTSD, the authors report. In addition to increased mortality risk, patients with PTSD reported more cardiac symptoms, including chest pain. However, clinical characteristics that typically account for survival differences in such patients did not differ between the 2 groups.

“Therefore, the perceived severity rather than the objective severity of a cardiac condition, as determined by cardiac criteria, may be associated with PTSD,” the authors write.

According to Dr. Ladwig, more research is needed to assess the behavioral and biologic pathways by which PTSD contributes to excess mortality risk in patients with ICDs.

  • Psychologic Disorders Common in Heart Patients

William T. Abraham, MD, director of the division of cardiovascular medicine at Ohio State University Medical Center, in Columbus, highlighted the need for high-quality psychologic support.

Dr. Abraham pointed out that psychologic disorders are common in patients with cardiovascular disease. At least 50% of heart failure patients are clinically depressed at some point in the natural history of their disease.

Depression in this setting and in the setting of other cardiovascular disorders, including ischemic heart disease and arrhythmias, said Dr. Abraham, is associated with worse outcomes. He also pointed out there is a pathophysiologic basis for this.

“Depression is associated with an increase in inflammatory mediators and other substances that may contribute to disease progression. PTSD is a little different and not uncommon following ICD shocks. However, the physiological effects of PTSD may be similar to those seen with depression. In its extreme form, shock-induced PTSD may lead some patients to ask that their ICDs be turned off. I have seen this more than a few times over the years. Counseling and support groups are very important in treating these patients,” he said.

References

  1. Arch Gen Psychiatry. 2008;65:1324-1330. Abstract

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Diabetes, Hypertension Affect Survival in Alzheimer’s Disease

November 27, 2008 at 12:12 am · Filed under Neurological section

The author: Professor Yasser Metwally

http://yassermetwally.com

INTRODUCTION

November 27, 2008 — A new prospective study shows that both a history of diabetes and a history of hypertension are independent predictors of a shorter lifespan after a diagnosis of Alzheimer’s disease (AD).

The findings are from a prospective population-based study looking at survival and the predictors of lifespan after diagnosis in a cohort of subjects who were free of dementia at baseline. The study was published in the November 4 issue of Neurology.

“Studies show that the average lifespan of a person diagnosed with Alzheimer’s disease can be anywhere from 3 to 9 years,” senior study author Yaakov Stern, PhD, from the Taub Institute for Research on Alzheimer’s Disease and the Aging Brain and director of the Cognitive Neuroscience Division of the Gertrude H. Sergievsky Center at Columbia University Medical Center, in New York City, said in a statement from the American Academy of Neurology (AAN).

“For that person and their caregiver, every minute counts,” he added. “Here we have 2 controllable factors that may drastically affect how long that person can survive.”

  • Unbiased Estimates

The most unbiased estimates of mortality and survival duration come from prospective population-based studies that start with dementia-free subjects and then actively screen for incident disease, the authors write, “yet few such studies have been undertaken in recent years, and these have been limited either by small sample sizes or ethnic homogeneity.”

This current study identified AD patients from the Washington Heights Inwood Columbia Aging Project, a longitudinal community-based study of cognitive aging in northern Manhattan. A total of 323 subjects, 65 years and older at baseline, were initially free of dementia and developed incident AD during study follow-up (an average of 4.1 years).

Factors associated with a shorter lifespan were examined using Cox proportional hazards models, with attained age as the time to event.

The authors report that the mortality rate was 10.7 per 100 person-years. Case-fatality rates were, not surprisingly, higher among those diagnosed at older ages and more than twice as high among non-Hispanic whites than among Hispanics.

The median lifespan of the entire sample was 92.2 years (95% CI, 90.3 – 94.1). “Although this longevity may seem remarkable, it is still 1 to 3 years less than the expected conditional lifespan based on populationwide life-table estimates, depending on age at diagnosis,” the authors write.

Factors found to be independently associated with shorter lifespan among those diagnosed with AD were a history of hypertension and a history of diabetes.

Table 1. Risk for Shorter Lifespan in AD Patients by Presence or Absence of Hypertension and Diabetes

Factor Hazard Ratio 95% CI
Hypertension vs no hypertension 2.57 1.04-6.37
Diabetes vs no diabetes 1.99 1.32-2.99

No differences were seen in lifespan by race or ethnicity after multivariable adjustment, but the median postdiagnosis survival duration was longer among Hispanics, with a median survival after diagnosis of 7 years, compared with 3.7 years for non-Hispanic whites and 4.8 years for African Americans.

“Although these findings were not significant, they are intriguing and warrant further research as to whether race affects survival time in people with AD,” Dr. Stern said in the AAN statement.

Interestingly, although comorbid hypertension and diabetes were more common among Hispanics, survival was longer in this group. “There is a growing [body of evidence] supporting a survival advantage among Hispanics in the United States, compared with other race/ethnic groups, which may be explained by ethnic differences in health-related behaviors, family networks, and social support,” the authors note. “Thus, our findings among Hispanics may reflect comparatively longer survival among all US Hispanics.”

References

  1. Neurology. 2008;71:1489-1495. Abstract

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Trigeminal neuralgia

November 25, 2008 at 4:16 am · Filed under Neurological section ·Tagged

The author: Professor Yasser Metwally

http://yassermetwally.com

INTRODUCTION

November 25, 2008 — Imagine having a jab of lightning-like pain shoot through your face when you brush your teeth or put on makeup. Sound excruciating? If you have trigeminal neuralgia, attacks of such pain are frequent and can often seem unbearable.

You may initially experience short, mild attacks, but trigeminal neuralgia can progress, causing longer, more frequent bouts of searing pain. These painful attacks can be spontaneous, but they may also be provoked by even mild stimulation of your face, including brushing your teeth, shaving or putting on makeup. The pain of trigeminal neuralgia may occur in a fairly small area of your face, or it may spread rapidly over a wider area.

Because of the variety of treatment options available, having trigeminal neuralgia doesn’t necessarily mean you’re doomed to a life of pain. Doctors usually can effectively manage trigeminal neuralgia, either with medications or surgery.

  • Signs and symptoms

An attack of trigeminal neuralgia can last from a few seconds to about a minute. Some people have mild, occasional twinges of pain, while other people have frequent, severe, electric-shock-like pain. The condition tends to come and go. You may experience attacks of pain off and on all day, or even for days or weeks at a time. Then, you may experience no pain for a prolonged period of time. Remission is less common the longer you have trigeminal neuralgia.

People who have experienced severe trigeminal neuralgia have described the pain as:

  1. Lightning-like or electric-shock-like
  2. Shooting
  3. Jabbing
  4. Like having live wires in your face

Trigeminal neuralgia usually affects just one side of your face. The pain may affect just a portion of one side of your face or spread in a wider pattern. Rarely, trigeminal neuralgia can affect both sides of your face, but not at the same time.

  • Causes

The condition is called trigeminal neuralgia because the painful facial areas are those served by one or more of the three branches of your trigeminal nerve. This large nerve originates deep inside your brain and carries sensation from your face to your brain. The pain of trigeminal neuralgia is due to a disturbance in the function of the trigeminal nerve. Trigeminal neuralgia is also known as tic douloureux.

The cause of the pain usually is due to contact between a normal artery or vein and the trigeminal nerve at the base of your brain. This places pressure on the nerve as it enters your brain and causes the nerve to misfire. Physical nerve damage or stress may be the initial trigger for trigeminal neuralgia.

After the trigeminal nerve leaves your brain and travels through the skull, it divides into three smaller branches, controlling sensation throughout your face:

  1. The first branch controls sensation in your eye, upper eyelid and forehead.

  2. The second branch controls sensation in your lower eyelid, cheek, nostril, upper lip and upper gum.

  3. The third branch controls sensations in your jaw, lower lip, lower gum and some of the muscles you use for chewing.

You may feel pain in the area served by just one branch of the trigeminal nerve, or the pain may affect all branches on one side of your face.

Besides compression from blood vessel contact, other less frequent sources of pain to the trigeminal nerve may include:

  1. Compression by a tumor

  2. Multiple sclerosis

  3. A stroke affecting the lower part of your brain, where the trigeminal nerve enters your central nervous system

A variety of triggers, many subtle, may set off the pain. These triggers may include:

  1. Shaving

  2. Stroking your face

  3. Eating

  4. Drinking

  5. Brushing your teeth

  6. Talking

  7. Putting on makeup

  8. Encountering a breeze

  9. Smiling

Trigeminal neuralgia affects women more often than men. The disorder is more likely to occur in people who are older than 50. About 5 percent of people with trigeminal neuralgia have other family members with the disorder, which suggests a possible genetic cause in some cases.

  • When to seek medical advice

Some people mistake the pain of trigeminal neuralgia for a toothache or a headache. It’s not uncommon for people to believe that their facial pain is dental-related, particularly when the pain seems to stem from the gumline or is located near a tooth.

If you experience facial pain, particularly prolonged pain or pain that hasn’t gone away with use of over-the-counter pain relievers, see your dentist or doctor.

  • Screening and diagnosis

If you go to your dentist, an examination of your mouth can reveal whether a problem with your teeth or gums is causing your pain.

If you go to your doctor, he or she will want to ask about your medical history and have you describe your pain — how severe it is, what part of your face it affects, how long pain lasts and what seems to trigger episodes of pain. You’ll also undergo a neurologic examination. During this examination, your doctor examines and touches parts of your face to try to determine exactly where the pain is occurring and — if it appears that you have trigeminal neuralgia — which branches of the trigeminal nerve may be affected.

Your doctor may exclude other possible conditions based on your medical history, the examination, and a magnetic resonance imaging (MRI) scan of your head.

  • Treatment

Medications are the usual initial treatment for trigeminal neuralgia. Medications are often effective in lessening or blocking the pain signals sent to your brain. A number of drugs are available. If you stop responding to a particular medication or experience too many side effects, switching to another medication may work for you.

  • Medications

Carbamazepine (Tegretol, Carbatrol). Carbamazepine, an anticonvulsant drug, is the most common medication that doctors use to treat trigeminal neuralgia. In the early stages of the disease, carbamazepine controls pain for most people. However, the effectiveness of carbamazepine decreases over time. Side effects include dizziness, confusion, sleepiness and nausea.

Baclofen. Baclofen is a muscle relaxant. Its effectiveness may increase when it’s used in combination with carbamazepine or phenytoin. Side effects include confusion, nausea and drowsiness.

Phenytoin (Dilantin, Phenytek). Phenytoin, another anticonvulsant medication, was the first medication used to treat trigeminal neuralgia. Side effects include gum enlargement, dizziness and drowsiness.

Oxcarbazepine (Trileptal). Oxcarbazepine is another anticonvulsant medication and is similar to carbamazepine. Side effects include dizziness and double vision.

Doctors may sometimes prescribe other medications, such as lamotrignine (Lamictal) or gabapentin (Neurontin).

Some people with trigeminal neuralgia eventually stop responding to medications, or they experience unpleasant side effects. For those people, surgery, or a combination of surgery and medications, may be an option.

  • Surgery

The goal of a number of surgical procedures is to either damage or destroy the part of the trigeminal nerve that’s the source of your pain. Because the success of these procedures depends on damaging the nerve, facial numbness of varying degree is a common side effect. These procedures involve:

Alcohol injection. Alcohol injections under the skin of your face, where the branches of the trigeminal nerve leave the bones of your face, may offer temporary pain relief by numbing the areas for weeks or months. Because the pain relief isn’t permanent, you may need repeated injections or a different procedure.

  • Glycerol injection

This procedure is called percutaneous glycerol rhizotomy (PGR). “Percutaneous” means through the skin. Your doctor inserts a needle through your face and into an opening in the base of your skull. The needle is guided into the trigeminal cistern, a small sac of spinal fluid that surrounds the trigeminal nerve ganglion (the area where the trigeminal nerve divides into three branches) and part of its root. Images are made to confirm that the needle is in the proper location. After confirming the location, your doctor injects a small amount of sterile glycerol. After three or four hours, the glycerol damages the trigeminal nerve and blocks pain signals. Initially, PGR relieves pain in most people. However, some people have a recurrence of pain, and many experience facial numbness or tingling.

  • Balloon compression

 In a procedure called percutaneous balloon compression of the trigeminal nerve (PBCTN), your doctor inserts a hollow needle through your face and into an opening in the base of your skull. Then, a thin, flexible tube (catheter) with a balloon on the end is threaded through the needle. The balloon is inflated with enough pressure to damage the nerve and block pain signals. PBCTN successfully controls pain in most people, at least for a while. Most people undergoing PBCTN experience facial numbness of varying degrees, and more than half experience nerve damage resulting in a temporary or permanent weakness of the muscles used to chew.

  • Electric current

A procedure called percutaneous stereotactic radiofrequency thermal rhizotomy (PSRTR) selectively destroys nerve fibers associated with pain. Your doctor threads a needle through your face and into an opening in your skull. Once in place, an electrode is threaded through the needle until it rests against the nerve root.

An electric current is passed through the tip of the electrode until it’s heated to the desired temperature. The heated tip damages the nerve fibers and creates an area of injury (lesion). If your pain isn’t eliminated, your doctor may create additional lesions.

PSRTR successfully controls pain in most people. Facial numbness is a common side effect of this type of treatment. The pain may return after a few years.

A procedure called microvascular decompression (MVD) doesn’t damage or destroy part of the trigeminal nerve. Instead, MVD involves relocating or removing blood vessels that are in contact with the trigeminal root and separating the nerve root and blood vessels with a small pad. During MVD, your doctor makes an incision behind one ear. Then, through a small hole in your skull, part of your brain is lifted to expose the trigeminal nerve. If your doctor finds an artery in contact with the nerve root, he or she directs it away from the nerve and places a pad between the nerve and the artery. Doctors usually remove a vein that is found to be compressing the trigeminal nerve.

MVD can successfully eliminate or reduce pain most of the time, but as with all other surgical procedures for trigeminal neuralgia, pain can recur in some people. While MVD has a high success rate, it also carries risks. There are small chances of decreased hearing, facial weakness, facial numbness, double vision, and even a stroke or death. The risk of facial numbness is less with MVD than with procedures that involve damaging the trigeminal nerve.

  • Severing the nerve

A procedure called partial sensory rhizotomy (PSR) involves cutting part of the trigeminal nerve at the base of your brain. Through an incision behind your ear, your doctor makes a quarter-sized hole in your skull to access the nerve. This procedure usually is helpful, but almost always causes facial numbness. And it’s possible for pain to recur. If your doctor doesn’t find an artery or vein in contact with the trigeminal nerve, he or she won’t be able to perform an MVD, and a PSR may be done instead.

  • Radiation

Gamma-knife radiosurgery (GKR) involves delivering a focused, high dose of radiation to the root of the trigeminal nerve. The radiation damages the trigeminal nerve and reduces or eliminates the pain. Relief isn’t immediate and can take several weeks to begin. GKR is successful in eliminating pain more than half of the time. Sometimes the pain may recur. The procedure is painless and typically is done without anesthesia. Because this procedure is relatively new, the long-term risks of this type of radiation are not yet known.

References

  1. Metwally, MYM: Textbook of neuroimaging, A CD-ROM publication, (Metwally, MYM editor) WEB-CD agency for electronic publication, version 9.2a April 2008 [Click to have a look at the home page]

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Case of the week…Multiple sclerosis presented clinically with bilateral trigeminal neuralgia and a high cervicomedullary active demyelinating plaque

November 25, 2008 at 4:09 am · Filed under Neurological section ·Tagged

The author: Professor Yasser Metwally

http://yassermetwally.com

INTRODUCTION

November 25, 2008 — In this case record professor Metwally discusses a case presented with the clinical diagnosis of trigeminal neuralgia due to multiple sclerosis and a high cervicomedullary active demyelinating plaque. The case is presented in downloadable PDF format.

16 years old female patient presented clinically with bilateral trigeminal neuralgia. The facial pain is more or less persistent or continuous, Dull or sharp with shooting sensations superimposed. The pain may extend outside trigeminal territory. The pain is occasionally provoked by touching the face, speaking, eating, or drinking. Clinical examination revealed some soft neurological signs such as diminution of the sensation on the left side of the face, bilateral extensor planter responses, unsustained horizontal nystagmus on the left side and diminution of deep sensation bilaterally. The patient was unaware of these neurological signs and was only complaining of trigeminal neuralgia.

Click here to download the case record in PDF format (314 KB)

Click here to download the short case version of this case record in PDF format (165 KB)

This case report illustrates that trigeminal neuralgia occasionally is associated with a serious systemic disease. Appropriate diagnostic tests are indicated for all patients with trigeminal neuralgia, since early diagnosis and treatment of an underlying systemic disease will have a significant impact on the prognosis.

  • Epidemiology of trigeminal neuralgia

Trigeminal neuralgia has an incidence of 4.5 per 100,000 population. The disorder is more prevalent among females (F:M sex ratio of 1.74:1) and affects primarily older people; the average age of onset is between the fifth and seventh decades. The majority of cases are unilateral; approximately 4 percent of cases are bilateral. TN most commonly involves either the maxillary or mandibular division of the trigeminal nerve alone, while the ophthalmic division rarely is affected alone. Involvement of more than one division of the trigeminal nerve is not uncommon.

Trigeminal neuralgia is characterized by spontaneous remissions that may last months or even years. Nevertheless, with time, pain attacks become more frequent, while remissions occur less often.

  • Definition of trigeminal neuralgia

Both the International Association for the Study of Pain (IASP) and International Headache Society (IHS) have suggested their own diagnostic criteria for trigeminal neuralgia. [1] These are remarkably similar and highlight the sudden, explosive nature of the pain (Table 1). In further descriptions of the condition, both classifications allude to vascular compression, MS and tumours as known aetiological causes. The IASP classification makes a distinction between trigeminal neuralgia (including MS) and secondary neuralgias (caused by structural lesions and injuries, but not including MS), while IHS separates idiopathic trigeminal neuralgia from the ‘symptomatic form’ depending on the presence of a structural lesion; it is not quite clear if vascular compression qualifies as such. Neither approach includes reference to variant forms of trigeminal neuralgia, which satisfy the diagnostic criteria but display additional features as well. [1]

Table 1 Definition of trigeminal neuralgia provided by the International Association for the Study of Pain, IASP1

IASP definition IHS definition

Sudden, usually unilateral, severe brief stabbing recurrent pains in the distribution of one or more branches of the Vth cranial nerve

Painful unilateral affliction of the face, characterized by brief electric shock like pain limited to the distribution of one or more divisions of the trigeminal nerve. Pain is commonly evoked by trivial stimuli including washing, shaving, smoking, talking, and brushing the teeth, but may also occur spontaneously. The pain is abrupt in onset and termination and may remit for varying periods

Slide sow 1. Case radiology

Click here to download the case record in PDF format (314 KB)

Click here to download the short case version of this case record in PDF format (165 KB)

References

  1. Metwally, MYM: Textbook of neuroimaging, A CD-ROM publication, (Metwally, MYM editor) WEB-CD agency for electronic publication, version 9.2a April 2008 [Click to have a look at the home page]

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Myotonia

November 25, 2008 at 4:01 am · Filed under Neurological section ·Tagged

The author: Professor Yasser Metwally

http://yassermetwally.com

INTRODUCTION

November 25, 2008 — Myotonia reflects a state of muscle fiber hyperexcitability. Impaired transmembrane conductance of either chloride or sodium ions results in myotonia. Myotonic disorders include the myotonic dystrophies and nondystrophic myotonias. Mutations in the genes encoding chloride (ClC-1) or sodium (SCN4A) channels expressed exclusively in skeletal muscle cause nondystrophic myotonias. Genetic defects in the myotonic dystrophies do not involve ion channel or its regulator proteins. Recent research supports a novel RNA-mediated disease mechanism of myotonia in the myotonic dystrophies. Myotonic dystrophy Type 1 is caused by CTG repeat expansion in the 3′ untranslated region in the Dystrophia Myotonica Protein Kinase (DMPK) gene. Myotonic dystrophy Type 2 is caused by CCTG repeat expansion in the first intron in Zinc Finger Protein 9 (ZNF9) gene. The expanded repeat is transcribed in RNA and forms discrete inclusions in nucleus in both types of myotonic dystrophies. Mutant RNA sequesters MBNL1, a splice regulator protein and depletes MBNL1 from the nucleoplasm. Loss of MBNL1 results in altered splicing of ClC-1 mRNA. Altered splice products do not encode functional ClC-1 protein. Subsequent loss of chloride conductance in muscle membrane causes myotonia in the myotonic dystrophies. The purpose of this review is to discuss the clinical presentation, recent advances in understanding the disease mechanism with particular emphasis on myotonic dystrophies and potential therapy options in myotonic disorders.

Video 1. Myotonia..This video shows delayed muscle relaxation which is a feature of Myotonia patients

Myotonia is the delayed relaxation of skeletal muscle fibers after voluntary muscle contraction. [1] Patients with myotonia may report painless muscle stiffness immediately upon initiating muscle activity after a period of rest. For example, inability to release hand grip after a strong handshake or trouble climbing stairs after a period of sitting. On physical examination, action myotonia can be elicited by isotonic muscle contraction such as asking the patient to make a tight fist or to grip and release the examiner’s fingers. Patients may have a lag in opening the eyes after initial tight eyelid closure. Myotonia improves with muscle exercise or repeated efforts, the so-called “warm-up phenomenon”. Percussion myotonia is a prolonged muscle contraction after mechanical compression of the muscle with a reflex hammer. Percussion of the thenar eminence results in prolonged adduction of the thumb, and percussion on the extensor digitorum communis in the forearm while the wrist is hanging down results in prolonged extension of the wrist.

Video 2. Myotonia Dystrophica…This video shows delayed muscle relaxation which is a feature of Myotonia patients

Clinical myotonia is the cumulative result of electrical hyperexcitability of individual muscle fibers. Needle Electromyography (EMG) reveals spontaneous runs of motor unit potentials with a characteristic waxing and waning frequency and amplitude [Figure 1]. The frequency may range from 20 to 150 mHz with amplitudes of the myotonic potentials in the 10 to 1000 mV range. Myotonic discharges produce an unforgettable unique sound similar to a motorcycle motor or World War II dive bomber or a chainsaw. By definition, myotonic discharges last 500 ms or longer and should be identified in at least three areas of an individual muscle outside of an endplate region. [2]

Figure 1. Electromyography (EMG) reveals spontaneous runs of motor unit potentials with a characteristic waxing and waning frequency and amplitude in Myotonic disorders (Click to enlarge figure)

Persistent depolarization of the myotonic muscle is due to abnormal expression of ion channels in the muscle membrane. Point mutations or deletions in the genes encoding either the sodium channel ( SCN4A ) or chloride channel ( CLCN1 ) expressed in skeletal muscle result in myotonia without muscle atrophy or degeneration, the so-called nondystrophic myotonias. [3,4] By contrast, DNA repeat expansion mutations causing myotonic dystrophies (DM) do not involve the ion channel or its regulatory proteins. Recent research has begun to unravel novel mechanisms of myotonia in DM. [5,6,7,8] This review will focus on the current understanding of the disease mechanisms and treatment in DM and the nondystrophic myotonias (see classification of myotonic disorders in [Figure 2]).

Figure 2. Classification of myotonic disorders (Click to enlarge figure)

References

1. Harper PS. Myotonic dystrophy, 3rd ed. London: W.B. Saunders; 2001.

2. Streib EW. Differential diagnosis of myotonic syndromes. Muscle Nerve 1987;10:603-15.

3. Heatwole CR, Moxley RT. The nondystrophic myotonias. Neurotherapeutics 2007;4:238-51.

4. Ryan AM, Matthews E, Hanna MG. Skeletal-muscle channelopathies: Periodic paralysis and nondystrophic myotonias. Curr Opin Neurol 2007;20:558-63.

5. Day JW, Ranum LP. RNA pathogenesis of the myotonic dystrophies. Neuromuscul Disord 2005;15:5-16.

6. Osborne RJ, Thornton CA. RNA-dominant diseases. Hum Mol Genet 2006;15:162-9.

7. Ranum LP, Cooper TA. RNA-mediated neuromuscular disorders. Ann Rev Neurosci 2006;29:259-77.

8. Wheeler TM, Thornton CA. Myotonic dystrophy: RNA-mediated muscle disease. Curr Opin Neurol 2007;20:572-576.

9. Brook JD, McCurrach ME, Harley HG, Buckler AJ, Church D, Aburatani H, et al. Molecular basis of myotonic dystrophy: Expansion of a trinucleotide (CTG) repeat at the 3′ end of a transcript encoding a protein kinase family member. Cell 1992;68:799-808.

10. Liquori CL, Ricker K, Moseley ML, Jacobsen JF, Kress W, Naylor SL et al. Myotonic dystrophy type 2 caused by a CCTG expansion in intron 1 of ZNF9. Science 2001;293:864-7.

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The Neuromuscular Junction

November 23, 2008 at 11:53 pm · Filed under Neurological section

The author: Professor Yasser Metwally

http://yassermetwally.com

INTRODUCTION

November 23, 2008 — The neuromuscular junction (NMJ) is a prototypic synapse although its structure is rather different from those of the central nervous system (CNS). The unmyelinated motor nerve terminals are separated from the postsynaptic membrane by a cleft that contains a basal lamina. This includes many proteins such as collagens, laminins, fibronectin and perlecan which help anchor some of the key elements involved in NMJ development and function; for instance acetylcholine esterase (AChE) is localized via ColQ, a collagen-like molecule, to the basal lamina. Agrin and neuregulins, secreted from the nerve terminal, are bound by the basal lamina and interact with their receptors, playing an important role in the location of postsynaptic membrane proteins, voltage-gated calcium channels and the dystroglycans. The postsynaptic membrane at the NMJ forms a series of deep folds. The acetylcholine receptors (AChRs) are found at the top one-third of these folds, whereas the voltage-gated sodium channels are anchored at the bottom of the folds. The development of the NMJ is a fascinating area of research [1] and many of the proteins involved are relevant to disease ([Figure 1] for a simple representation).

Figure 1. The Neuromuscular Junction (Click to enlarge figure)

The nerve action potential opens voltage-gated calcium channels (VGCCs) that are located in the motor nerve terminal [Figure 1]. The resulting influx of calcium leads to the release of about 30 (in human muscle) individual packets of acetylcholine (ACh). Some of the ACh is hydrolysed by AChE but about 65% reaches the AChRs on the postsynaptic membrane. Binding of two ACh to each AChR leads to the opening of the AChR-associated ion channel, influx of cations (mainly sodium) and generation of an endplate potential (EPP). The EPP in normal human muscles is around 20-30 mV. Miniature EPPs (MEPPs) are the result of the spontaneous release of single packets of ACh and their amplitudes are much smaller (around 1 mV) and generally reflect the density of functional AChRs.

The EPP rapidly depolarises the postsynaptic membrane and, when this reaches a critical firing threshold, the voltatge-gated sodium channels open and an action potential is propagated along the muscle fiber leading to contraction. The extent to which the EPP exceeds that necessary to initiate the action potential is usually called the safety factor for neuromuscular transmission. [2] The EPP is short-lived because the AChRs close spontaneously, ACh dissociates and escapes by diffusion or is hydrolysed by AChE. The calcium channels also close spontaneously. Opening of voltage-gated potassium channels on the presynaptic membrane is important in restoring the membrane potential and limiting calcium channel opening.

References

1. Sanes JR, Lichtman JW. Induction, assembly, maturation and maintenance of a postsynaptic apparatus. Nat Rev Neurosci 2001;2:791-805.

2. Wood SJ, Slater CR. Safety factor at the neuromuscular junction. Prog Neurobiol 2001;64:393-429.

3. Hodgson WC, Wickramaratna JC. In vitro neuromuscular activity of snake venoms. Clin Exp Pharmacol Physiol 2002;29:807-14.

4. Drachman DB. Myasthenia gravis. N Engl J Med 1994;330:1797-810.

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Traumatic lesions of brain parenchyma… Diffuse axonal injury (DAI)

November 23, 2008 at 3:10 pm · Filed under Neurological section ·Tagged

The author: Professor Yasser Metwally

http://yassermetwally.com

INTRODUCTION

November 23, 2008 — Diffuse axonal injury is a special traumatic lesion caused by  sudden angular rotation of the brain.  It occurs most frequently in motor vehicle accidents and following blows to the head and less frequently with falls. In the course of such head injuries, the brain, which has a jelly-like consistency, goes into a violent swirling motion that stretches axons. Axons do not snap from this initial injury; their sudden deformation causes changes in the axonal cytoskeleton (compaction of neurofilaments, loss of neurotubules) that lead to an arrest of the fast axoplasmic flow. Components of this flow, including mitochondria and other organelles, accumulate proximal to the lesion and cause axonal swellings. Some axons with mild lesions probably recover but many rupture. It takes several hours from trauma to axonal rupture. The cascade of reactions that lead to the formation of axonal swellings is probably initiated by influx of calcium through the stretched axolemma. The swellings are located at nodes of Ranvier where the axolemma is more liable to deform because there is no myelin. Brain damage is most severe along midline structures (corpus callosum, brainstem) where shear forces are greatest and at the cortex-white matter junction because of the change in the consistency of brain tissue.

Click here for a video clip on Diffuse axonal injury (DAI)

Clinically, patients with severe DAI become unconscious immediately after the injury and either remain comatose or go into a persistent vegetative state. Cerebral concussion is thought to be a mild form of DAI without permanent pathology. The loss of consciousness in concussion is probably due to a functional disturbance of the reticular activating substance of the upper brainstem. DAI within the medulla leads to cardiorespiratory arrest. In severe TBI, DAI is compounded by widespread vascular injury and other traumatic lesions which cause cerebral edema and HIE.

Grossly, the brain in DAI is either normal or shows petechial hemorrhages in the corpus callosum, centrum semiovale, dorsolateral brainstem, and other areas, due to tearing of blood vessels. Microscopically, the cerebral white matter shows  axonal swellings (diffuse or in clusters).

Figure 1. A, The brain in DAI is either normal or shows petechial hemorrhages in the corpus callosum, centrum semiovale, dorsolateral brainstem, and other areas, due to tearing of blood , vessels. B, Microscopically, the cerebral white matter shows  axonal swellings (diffuse or in clusters). (Click to enlarge figure)

These can occur anywhere but are particularly common in the parasagittal parts of the brain, the corpus callosum, fornix, internal capsule and the brain stem. Axonal swellings can be detected with H&E and silver stains 15 hours after injury. Immunostains with antibodies to Beta Amyloid Precursor Protein (BAPP) can detect the axonal lesions in 2-3 hours after injury. BAPP is produced by neurons as a reaction to injury and normally flows down the axon and accumulates proximal to the lesions.   Axonal swellings may persist for years.  Distal to the swellings, axons degenerate, causing white matter atrophy and gliosis. 

References

  1. Metwally, MYM: Textbook of neuroimaging, A CD-ROM publication, (Metwally, MYM editor) WEB-CD agency for electronic publication, version 9.2a April 2008 [Click to have a look at the home page]

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