Devon Schuyler

Vision Restoration Therapy (VRT) is an FDA-cleared device for treatment of visual field defects caused by stroke or traumatic brain injury. The therapy works by stimulating the brain to form new connections, according to NovaVision, the device's manufacturer. But critics maintain that VRT is nothing more than a pricey way to promote saccadic eye movement.

Jose G. Romano, MD, associate professor of neurology at the University of Miami, who serves on Nova- Vision's Scientific and Medical Board of Advisors, said that VRT has been shown to increase the visual field by about 5 degrees. "The improvements are likely due to cortical reorganization," he added.

But Victoria S. Pelak, MD, associate professor of neurology and ophthalmology at the University of Colorado Health Sciences Center in Aurora, who wrote a recent review on treating visual field defects,

 said that there are a "lot of holes" in both the results and the purported mechanism behind them. For example, most studies are able to detect positive results only when using a measure of the visual field developed by the inventors of VRT. Even if the therapy does work, she said, it is likely that the benefit derives from adaptive strategies, not neuroplasticity.

"I think that VRT very likely does train a person to increase attention to a blind spot," Pelak said. "But the way the company has gone about marketing it, claiming it does more than it really can, is something that has been bothersome to a lot of people."

VRT is available at about 50 centers in the United States; about 1000 persons have been treated at these centers so far. The treatment is for persons with visual field defects, such as homonymous hemianopia. Patients with ocular or cerebral disease or significant cognitive defects are not candidates for the therapy.

After screening in a doctor's office, eligible patients receive a personalized laptop computer device for home use. Therapy involves viewing a monitor that flashes light stimuli in the area of residual vision between the scotoma and the intact visual field. The user is instructed to press a button each time these stimuli appear.

The device keeps the user's eyes centered by presenting a fixation target that requires the user to press a button each time the target changes color. "If you move your eyes, it's hard to detect the change," said Romano.

Therapy involves two 30-minute treatment sessions a day, 6 days a week, for 6 months. The device re-maps the user's vision each month, and the results are sent to NovaVision for analysis and adjustment of the treatment plan.

"The new plan accounts for shifting of the border between sight and blindness," said Romano. "Or, if there's no improvement, there might be a need for a new treatment paradigm," he said. Adjustments may include changing the pattern of stimuli presentation, increasing or decreasing the intensity of the stimuli, or changing the color or form of the stimuli.

In a 161-person study that Romano presented at the American Academy of Neurology meeting in Boston last May, 76% of patients with homonymous visual field defects benefited from the therapy.

 The average increase in visual field was about 5 degrees, which he said was consistent with previous studies. For example, in a study by Kasten and colleagues,

 VRT expanded the visual field by an average of 4.9 to 5.8 degrees.

"Five degrees may not sound like much, but it can be very significant," Romano said. He pointed out that reading takes place in the central 5 degrees of vision, so that losing or gaining just half of that can have a sizable effect on such daily activities besides reading as using a computer or watching television.

Although the exact mechanism behind the improvement is unclear, Romano said that some type of neuroplasticity is involved. "It could be the reconnection of surviving neurons, but more likely it is either increased attention to the border between the seeing and blind fields or the activation of previously underused pathways to bypass damaged areas in the brain," he suggested.

Is is unlikely that saccades could explain the vision improvement, Romano said, citing a recent study by Kasten and colleagues

 that accounted for eye movement. In this study, the researchers used a 2D Eye Tracker (Chronos Vision) to monitor eye position perimetry testing. The researchers found that eyes remain within 2 degrees of fixation 98.9% of the time. "I thought this paper was convincing," said Romano.

Pelak, however, dismissed the idea that neuroplasticity could explain the vision improvements. "It probably has more to do with the person's attention-being able to make very, very small movements of their eye-to detect these areas," she said. She pointed out that just 2 degrees of movement could account for the improvement with VRT.

Romano said that if the eye movements were within 2 degrees, they would be too small to explain the 5 degree shift in the visual field defect. But Pelak pointed out that the articles in peer-reviewed journals do not support a 5-degree shift: "Five degrees is constantly claimed, but it is nearly always 2 degrees or less if any improvement is found at all with threshold testing."

Another argument against neuroplasticity, Pelak said, is the fact that vision improvements occur only in the central visual field. "They stimulate other areas beyond the central 5-degree field if the person's vision loss begins at 6 degrees away, so why don't these patients show improvement?" she asked. She added that if neuroplasticity were occurring, it should occur in the peripheral areas as well as in the central ones. "Why isn't there something out 15 degrees?" she asked.

She also took exception to Romano's statement that early data from Julkunen and colleagues

 of imaging studies with positron emission tomography and functional MRI support the concept of neuroplasticity because they have shown functional changes in the brain after visual stimulation.

"That's a huge can of worms [for NovaVision] because those types of imaging studies have not been proved to represent neuronal plasticity," said Pelak. "These could be the normal changes that take place when your brain gets trained to do something."

Pelak also objected to the use of high-resolution perimetry (HRP)-which was developed by Sabel and Kasten, the researchers who developed VRT-to measure improvements. Unlike a standard threshold visual field test like Tübinger automatic perimetry (TAP), which measures the ability to see gradually brighter stimuli, HRP is a suprathreshold test that presents only very bright stimuli. This type of test may allow peripheral retinal loci to detect light. "There is no analogous visual field machine that's used in the practice of ophthalmology or neuro-ophthalmology," she said.

In addition, Pelak pointed out the inherent credibility problem in having the same researchers design both a product and the device used to evaluate it. In fact, the evidence suggests that standard measures are unable to detect a benefit with VRT.

For example, in a study of 19 patients with post- chiasmal injury, HRP detected improvements in the average number of correct responses and the visual field border position, whereas TAP detected no improvements.

 In a companion study of 19 patients with optic nerve injury, the visual field expanded by 5.8 degrees when measured by HRP but only 2.1 degrees when measured by TAP.

In addition, 3 studies that looked at the same set of 16 or 17 patients revealed different results depending on whether HRP, scanning laser ophthalmoscopy (SLO), or TAP was used. Sabel and colleagues

 found that the visual field increased by an average of 1.73 degrees and that the average number of correct responses had increased from 63% to 69% when measured by HRP. When Schreiber and colleagues

 published data on the same patients, however, they reported that only 2 patients experienced more than 2 degrees of enlargement of the visual field using TAP-and the improvements were in just 1 eye. Reinhard and colleagues,

 using SLO, also found that VRT was not effective: the visual field border had shifted in just 1 of 34 eyes after 6 months of treatment.

Romano countered that the Reinhard study is just one of many and that SLO testing is not a good measure of improvement in patients with visual field defects. "The task required to complete the SLO is too difficult for these persons and, therefore, absence of improvement in SLO does not negate the ability to respond to less difficult tasks presented in other types of perimetries," he said.

Pelak also said that VRT has never been shown to improve function. "The jury is still out on whether it causes functional improvement. The company says that it does, but studies that are more independent have not shown those types of results," she said.

 did find a slight increase in reading speed with VRT. Romano also pointed to a retrospective analysis by Mueller and colleagues

 in which 88% of 69 patients receiving VRT reported subjective improvements in activities of daily living, specifically "carrying out hobbies" and "general improvement in vision." But Pelak pointed out that the patients did not improve on most of the subjective measures in this study and that the improvements that did occur failed to correspond with the changes on HRP-an admission that the study authors make themselves.

Vision restoration therapy typically costs about $6000 and is not covered by insurance. Pelak said that insurers are justified in denying coverage for the treatment because it has not been proved to work. The product was cleared by the FDA on the basis of it being "functionally equivalent" to 2 other vision devices on the market. The FDA has never reviewed data on VRT's effectiveness. Romano, however, said that $33 a day is right in line with other rehabilitative interventions and that NovaVision is working with Medicare to obtain reimbursement.

There is one point on which the 2 researchers agree: that the introduction of VRT has increased awareness of visual field defects.

"It's nice to get it out there that there are treatments for this," said Pelak. She said that physical and occupational therapy can help persons learn to compensate for their deficits and that some people find special prism glasses to be helpful. "But the treatment that seems to have the most potential is eye movement training," she said. She pointed to a visual rehabilitation strategy designed by Spitzyna and colleagues

that involves 400 minutes of therapy over 4 weeks on a free Web site (

www.ucl.ac.uk/mediares/mm/mm-projects/neurology/read_right

). She added that further research is needed to determine whether such training can improve persons' lives.  

 Pelak VS, Dubin M, Whitney E. Homonymous hemianopia: a critical analysis of optical devices, compensatory training, and NovaVision. 

 Romano JG, Schulz P, Kenkel S, Todd DP. Visual field changes after Vision Restoration Therapy (VRT). Presented at: 59th Annual Meeting of the American Academy of Neurology; May 2, 2007; Boston.


 Kasten E, Wust S, Behrens-Baumann W, Sabel BA. Computer-based training for the treatment of partial blindness. 

 Kasten E, Bunzenthal U, Sabel BA. Visual field recovery after vision restoration therapy (VRT) is independent of eye movements: an eye tracker study. 

 Julkunen L, Tenovuo O, Vorobyev V, et al. Functional brain imaging, clinical and neurophysiological outcome of visual rehabilitation in a chronic stroke patient. 

 Sabel BA, Kenkel S, Kasten E. Vision restoration therapy (VRT) efficacy as assessed by comparative perimetric analysis and subjective questionnaires. 

 Schreiber A, Vonthein R, Reinhard J, et al. Effect of visual restitution training on absolute homonymous scotomas. 

 Reinhard J, Schreiber A, Schiefer U, et al. Does visual restitution training change absolute homonymous visual field defects? A fundus controlled study. 

 Mueller I, Poggel DA, Kenkel S, et al. Vision Restoration Therapy after brain damage: subjective improvements of activities of daily life and their relationship to visual field enlargements. 

 Spitzyna GA, Wise RJ, McDonald SA, et al. Optokinetic therapy improves text reading in patients with hemianopic alexia: a controlled trial. 

Articles

Experts Debate Usefulness of Vision Restoration Therapy

"People are getting excited about apathy nowbecause it may be a behavioral marker for amore rapidly progressing dementia," saidPrasad Padala, MD, assistant professor ofpsychiatry at the University of NebraskaMedical Center in Omaha.

A recent 4-year study linked apathy to a hastened decline in persons with Alzheimer disease (AD).

 Another recent study found that persons with mild cognitive impairment (MCI) were more likely to convert to AD a year later if they also had apathy.

Another factor that has increased interest in apathy is the growing understanding of physical changes in the brain. For example, an autopsy study found that among persons with AD, those who had chronic apathy tended to have more neurofibrillary tangles than those without apathy.

 Clinically apathetic persons with dementia may even have a different genetic makeup than persons with dementia who are not apathetic. A recent study showed that persons with AD were more likely to be carriers of the ApoE e4 allele if they also had apathy.

Apathy traditionally has received less attention than other neuropsychiatric states in dementia, such as depression, agitation, aggression, and psychosis. This is slowly changing. Although researchers are becoming more knowledgeable about the condition, treating it remains difficult. "There aren't many medications or other treatments that have shown efficacy in treating apathy," said Tiffany Chow, MD, assistant professor of neurology and geriatric psychiatry at the University of Toronto. But given the new interest in the condition, researchers expect full-scale randomized controlled trials to follow.

Apathy, which refers to a loss of motivation, is marked by such characteristics as diminished initiation, poor persistence, lack of interest, indifference, low social engagement, blunted emotional re- sponse, and lack of insight.

 It is the most common behavioral disturbance in dementia. Prevalence rates are as high as 80% in clinic samples of patients with primary dementia and range from 27% to 36% in community samples.

 An analysis of 3 European studies produced a mean of about 56%.

 The incidence of apathy increases with the severity of the dementia.

"In the beginning stages of dementia, people may withdraw from activities because they're aware of what's going on and want to avoid making themselves look bad," said Chow. "Then in the moderate to severe stages, they do shut down and are not able to initiate their own activities."

Apathy has a dramatic effect on persons with dementia and their families. First, the condition leads to decreased function. In one study, persons with apathy were nearly 3 times more likely than those without apathy to be impaired in dressing, bathing, transferring from bed to chair, using the toilet, walking, or eating and more than 3 times more likely to be impaired in all 6 activities.

Second, apathy is linked to executive cognitive dysfunction. For example, a study of 184 patients with probable AD found that apathetic patients had significantly poorer performance in naming, word-list learning, verbal fluency, and set-shifting than those without apathy.

 "Without interest or initiative, it's difficult for these patients to use their remaining cognitive function," said Philippe Robert, MD, director of the Memory Center for Care and Research at Nice University Hospital in France.

Third, apathy makes persons less likely to comply with treatment. This can lead to setbacks in treatment not only for dementia but also for concomitant health conditions. Finally, the extreme burden on caregivers created by these deficits tends to increase caregiver distress. "People with apathy tend to depend a lot more on caregivers, even for things they can do on their own," said Padala. Although it has not been proved in studies, patients with apathy may require hired home care and institutional care earlier than other patients with dementia.

Apathy may pack an additional punch for caregivers who are family members because it chips away at the patient's personality. "The caregiver sees the person withdrawing and shutting down, and it seems like they're fading into the distance right before their eyes," said Chow. "A lot of family members say that they prefer someone doing obsessive-compulsive things to just being apathetic," she added.

The situation may be different in a nursing home, where apathetic patients who sit quietly and do not cause disturbances might be viewed as easy to care for. "If I were working in a nursing home, I would probably not be perturbed by apathetic patients as much as by someone who is having active hallucinations," said Padala. This may be one reason why apathy research has traditionally received less funding than research on problems such as agitation and psychosis.

Conducting research on apathy requires an accurate measurement scale. The most often used scales for measuring apathy in dementia are the Apathy Evaluation Scale (AES), the apathy subscale of the Neuropsychiatric Inventory (NPI), and the Apathy Inventory (IA).

The AES is an 18-item scale that has separate versions for the patient, informant, and clinician. It measures 3 clinical dimensions of apathy: emotional blunting, lack of interest, and lack of initiative. The IA also has 3 versions and measures 3 clinical dimensions but is shorter than the AES. The NPI, which is a long test that is used widely in drug trials, measures 10 common behavioral disturbances in persons with dementia and other neurological disorders. The informant supplies answers to 4 questions related to apathy; a positive response to 1 triggers a subset of 8 more specific questions on apathy.	

Other scales include Starkstein's 14-item scale, the Irritability-Apathy Scale, the Cambridge Behavioral Inventory (CBI), and the Lille Apathy Rating Scale (LARS). The Starkstein scale is similar to the AES but shorter. The Irritability-Apathy Scale is a brief, informant-based scale with 5 items related to apathy that is designed for use in persons with AD or Huntington disease. The CBI is an informant-based scale that measures neuropsychiatric symptoms and functional ability in dementia. The LARS is long, with 33 items, but is designed for simplicity because it requests "yes" and "no" answers instead of ratings on a numbered scale.

Diana E. Clarke, PhD, psychiatric epidemiologist in the Department of Mental Health at the Johns Hopkins Bloomberg School of Public Health in Baltimore, said that based on her assessment of the AES, "informant- and clinician-rated scales are better than self-rated scales."

"As a screening for whether apathy is present, I think that any of the scales are fine," said Chow. However, comparative studies are needed to see which scales are best at measuring apathy, which is important for treatment studies.

Chow pointed out that it can be difficult to detect apathy in office visits because they are brief, lasting only about 15 or 20 minutes, and many patients are more alert in a medical office. "It drives the families crazy, because they say that the person doesn't respond all day at home and then he's fine in the office." She said this is why it is important for the neurologist or neuropsychiatrist to ask family members whether the person is keeping up with usual activities.

Apathy also correlates with physical changes in the brain. In addition to the recent autopsy study that found a link between chronic apathy and neurofibrillary tangles in persons with AD, another study found that among 31 persons with AD, those with low initiative and interest scores had significantly reduced perfusion in the right anterior cingulate cortex on a single photon emission CT scan compared with those who had normal scores.

Depression, although not as prevalent, is another condition that is commonly seen in patients with dementia. Apathy and depression have some overlapping characteristics--namely, loss of interest or pleasure in activities. Both are associated with functional and cognitive decline. As a result, the conditions can be confused with each other. To complicate matters, many patients have both apathy and depression.

In the Cache County Study on Memory, Health, and Aging, which looked at more than 5000 persons aged 65 years and older, about 42% of persons with apathy had depression and about 37% of those with depression had apathy.

 In the European Alzheimer's Disease Consortium study, which analyzed more than 3000 persons with AD, 22% of the participants had apathy alone, 10% had depression alone, and 15% had apathy and depression.

There are many important differences between apathy and depression, however. "Apathy relates more to indifference, whereas depression is more hopelessness about the future," said Padala. Apathy and depression also look very different in the brain. For example, a recently published study of 84 older persons found that those who were depressed had smaller gray matter volumes in the orbitofrontal areas as measured by MRI, whereas those with apathy had decreased gray matter volume in the right anterior cingulate cortex.

 The more severe the apathy, the smaller the gray matter volume.

Differentiating between apathy and depression is important because the treatment approaches are different. For example, Padala pointed out that selective serotonin reuptake inhibitors used for treatment of depression, such as fluoxetine (Prozac) and sertraline (Zoloft), may actually contribute to apathy. "One of my patients explained to me that after he started the medication, he no longer felt depressed, but he also didn't feel anything else," Padala commented.

Conversely, the stimulant methylphenidate (Ritalin), which appears to be helpful in treating apathy, is not effective in depression.

Investigators are now finding links between apathy and MCI. One study found that among persons with MCI, those in whom AD developed at 1-year follow-up were significantly more likely to have symptoms of apathy at baseline (92%) than those in whom AD did not develop (27%).

 that his 3-year results, which have been submitted for publication, continue to show that the presence of apathy increases the risk of conversion to AD for persons with MCI.

"The presence of lack of interest--a soft behavioral sign that's easy to detect during a clinical interview--could indicate potential decline in patients with MCI," said Robert. "It's important to carefully check the cognitive status of these patients."

In addition, the Cache County Study of Memory and Aging found that clinical apathy was more common in persons with a mild cognitive syndrome (3.1%) than in those who were cognitively normal (1.4%), although not as common as in persons with dementia (17.3%).	

The treatment of apathy in dementia is still in its infancy, and it is unclear which treatments are effective. "Our knowledge has been limited by a lack of clinical trials," said Clarke.

Some recent research has focused on cholinesterase inhibitors, but results have been mixed. "Cholinesterase inhibitors help in some cases, but not in the majority," said Chiadi Onyike, MD, assistant professor of psychiatry and behavioral sciences at Johns Hopkins University.

Several studies have analyzed the cholinesterase inhibitor donepezil (Aricept) for treatment of apathy in AD, with varying results. One 6-month, randomized, double-blind, placebo-controlled trial in 290 outpatients with AD found that donepezil significantly reduced apathy, depression, and anxiety.

 By contrast, a placebo-controlled study in 208 nursing home patients reported that although donepezil significantly reduced agitation, it did not reduce apathy.

 It is possible that donepezil may be more effective for treating apathy in mild to moderate AD than in late-stage AD, but further studies are needed.

Two 6-month, open-label prospective studies in nursing home patients have looked at the drug rivastigmine (Exelon). The first study, which involved 669 patients with moderate to severe AD, found an improvement in apathy at 3 months but only a trend toward reduced apathy at 6 months. The second study of 173 patients with moderate to severe AD found an improvement in neuropsychiatric symptoms overall but no improvement in apathy.

Galantamine (Razadyne) improved the condition of patients with apathy and anxiety in a 6-month, placebo-controlled, double-blind study of nearly 600 patients with mild to moderate AD.

However, a pooled sample of more than 2000 patients with mild to moderate AD found that galantamine did not improve a combined end point that included effects on hallucinations, anxiety, apathy, and aberrant motor behaviors.

A small case series of 3 patients with frontotemporal dementia found that their apathy improved with memantine (Namenda).

Researchers have also tried stimulants such as methylphenidate, dextroamphetamine (Adderall), and modafinil (Provigil) in persons with apathy and dementia. Padala has reported positive results with the use of methylphenidate in a small case series

Onyike said that amantadine (Symmetrel), bromocriptine (Parlodel), and bupropion (Wellbutrin) may be useful in some cases.

The research on nonpharmacological interventions for apathy in dementia is even sparser than that for pharmacological interventions. One study found that persons with dementia and apathy were engaged by live music.

 An Italian study of elderly persons, most of whom had dementia, suggested that validation therapy improved apathy.

 Other treatments that have been used to treat apathy include Snoezelen (multisensory stimulation) and aromatherapy.

 Onyike said that structured activity programs that socialize the person who is living in a residential community could be useful; another approach is to have the caregiver oversee a regimen of brief focused activities and interpersonal interactions.

"Neurologists and neuropsychiatrists are becoming increasingly aware of apathy in dementia and its consequences on the course of the illness and its impact on caregivers," said Clarke. However, she added that "more research is needed . . . to improve our knowledge of the biology and genetics of apathy and dementia and enhance treatment strategies."

Onyike agreed that researchers need to develop a better understanding of apathy. "How does a person develop drive, become aware of it, and initiate actions based on the drive?" he asked. He said that researchers could attempt to answer this question and then work to define the brain circuitry that underlies the process. Robert van Reekum, MD, assistant professor of psychiatry at the University of Toronto, agreed that researchers "need a comprehensive biopsychosocial understanding of motivational behavior." van Reekum said that future research also should involve testing the validity of the upcoming 

 diagnosis of apathy, developing and testing measurement tools, conducting randomized controlled trials of promising interventions, and investigating the possibility of various subtypes of apathy.

Chow agreed, saying that a problem with treatment approaches is that "we haven't spent enough time parsing the type of apathy that we're trying to treat." It is possible, for example, that persons with affective apathy might be more likely to respond to antidepressants; those with cognitive apathy might be more responsive to cholinesterase inhibitors. "Until we separate patients out into these different groups, then maybe the drug trials haven't been properly conducted," she said.   

 Starkstein SE, Jorge R, Mizrahi R, Robinson RG. A prospective longitudinal study of apathy in Alzheimer's disease.

 Robert PH, Berr C, Volteau M, et al, the PreAL study. Apathy in patients with mild cognitive impairment and the risk of developing dementia of Alzheimer's disease: a one-year follow-up study. 

 Marshall GA, Fairbanks LA, Tekin S, et al. Neuropathologic correlates of apathy in Alzheimer's disease. 

 Monastero R, Mariani E, Camarda C, et al. Association between apolipoprotein E epsilon4 allele and apathy in probable Alzheimer's disease. 

 Landes AM, Sperry SD, Strauss ME, Geldmacher DS. Apathy in Alzheimer's disease. 

 Onyike CU, Sheppard JM, Tschanz JT, et al. Epidemiology of apathy in older adults: the Cache County Study. 

 Robert PH, Verhey FR, Byrne EJ, et al. Grouping for behavioral and psychological symptoms in dementia: clinical and biological aspects. Consensus paper of the European Alzheimer disease consortium. 

 Freels S, Cohen D, Eisdorfer C, et al. Functional status and clinical findings in patients with Alzheimer's disease. 

 Kuzis G, Sabe L, Tiberti C, et al. Neuropsychological correlates of apathy and depression in patients with dementia. 

 Clarke DE, Reekum R, Simard M, et al. Apathy in dementia: an examination of the psychometric properties of the apathy evaluation scale. 

 Robert PH, Darcourt G, Koulibaly MP, et al. Lack of initiative and interest in Alzheimer's disease: a single photon emission computed tomography study. 

 Robert PH, Byrne J, Aalten P, et al. Apathy and depressive symptoms in Alzheimer's disease. Results from the European Alzheimer's Disease Consortium.

 Alzheimer's Dementia J Alzheimer's Assoc. 

 Lavretsky H, Ballmaier M, Pham D, et al. Neuroanatomical characteristics of geriatric apathy and depression: a magnetic resonance imaging study. 

A recent 4-year study linked apathy to a hastened decline in persons with Alzheimer disease (AD). Another recent study found that persons with mild cognitive impairment (MCI) were more likely to convert to AD a year later if they also had apathy.

Recognition of Apathy as Marker for Dementia Growing

Five words that are guaranteed to annoy your patient with a diagnosis of psychogenic movement disorder (PMD) are "It's all in your head."

"It's the worst thing you can say," said Katie Kompoliti, MD, associate professor of neurological sciences at Rush University Medical Center in Chicago. Patients who hear this are likely to reject the diagnosis and seek further opinions; some will visit half a dozen specialists or more. They can run up thousands of dollars in health care costs and be subjected to unnecessary drug regimens and risky procedures.

"Patients can end up worse than they were at the onset of the disorder," said Joseph Jankovic, MD, professor of neurology and director of the Movement Disorders Clinic at Baylor College of Medicine in Houston. Finally, their chances of recovery appear to decrease the longer their condition goes untreated. This is why it is essential to make an accurate diagnosis in a reasonable amount of time and to deliver the news with sensitivity. The good news? Patients who accept their diagnosis and follow through with treatment have a good chance of recovery.

"It's a very difficult diagnosis," said Vanessa K. Hinson, MD, director of the Movement Disorders Program at the Medical University of South Carolina in Charleston. "But it's so important to make it, because if you do, these patients can get better."


A patient with a PMD may exhibit any of the movements seen in organic movement disorders, including tremor, dystonia, chorea, bradykinesia, myoclonus, tics, athetosis, ballism, and lack of coordination. The person may also have disrupted speech and gait.

The most common cause of PMD is a conversion disorder, in which psychological stressors cause the person to experience physical symptoms. The second most common cause is somatization disorder, in which the person seeks medical attention for recurrent and changing somatic complaints. Neurologists need to remember that the symptoms of conversion and somatization disorders are not under the person's conscious control.

A less common cause is factitious disorder, in which the person achieves a psychological gain from his or her disease. As with conversion disorder and somatization disorder, persons with factitious disorder generally do not produce their symptoms intentionally, although some patients are malingerers, meaning that they produce their symptoms intentionally to achieve financial or other gain. Malingering is the least common cause of the disorder.

Patients with PMD account for an estimated 2% to 3% of those in movement disorder clinics,

 and some centers report even higher rates. For example, about 15% of patients evaluated in the Baylor College of Medicine Movement Disorders Clinic have a psychogenic cause for their symptoms.

"I think the reason [for the high rates at our center] is that community neurologists recognize the common movement disorders and refer the atypical ones to movement disorder centers," said Jankovic. "Many, if not most, of these cases turn out to be psychogenic."	

The average age at onset ranges from 37 to 50 years, and women account for more than half of cases-estimates range from 61% to 87%.

 Although they usually occur alone, 10% to 15% are associated with organic neurological disorders.

 Many patients have a coexisting axis I diagnosis, such as major depression or an anxiety disorder, or an axis II diagnosis, such as personality disorder.

Known risk factors for PMD include a history of sexual abuse or rape, surgery or other physical trauma, and highly emotionally stressful life events.


Jankovic said that he is seeing more cases of PMD than ever before, probably because the disease is being recognized more frequently. "In the past, cases would often be misdiagnosed," he said.

Neurologists have plenty of ways to make the diagnosis, however. Hinson emphasized that there are specific clinical characteristics that the neurologist should be looking for and that the diagnosis should not be viewed as a diagnosis of exclusion.

For example, PMDs tend to come on abruptly. "It will often be very specific; the patient will tell me, 'I was sitting in the fourth row of church, it was 10:30 in the morning, I felt a cold sweat on my face, my arm started shaking,'" said Kompoliti. The symptoms will also progress quickly, which is unusual in an organic movement disorder.

The onset is often related to a precipitating event, such as surgery, the death of a loved one, divorce, rape, or financial stress. "The person basically starts having a multitude of abnormal movements right after this precipitating event," said Hinson.

There are also typical clinical signs. For example, the movements tend to be incongruent with organic disease, and there may be multiple abnormal movements. "So I might see a patient who has tremor and myoclonus and chorea and on top of that, a speech and a gait disorder," said Hinson.

The movements tend to exhibit distractibility and variability and increase with attention to the affected body part. "The movements may vary throughout the examination," said Hinson. "When the examiner leaves the room, the movement improves, and when we pay special attention to the limb in question, the movement suddenly is exacerbated."

Other characteristics are deliberate slowness of movement; entrainment; coactivation; association with false weakness, sensory loss, and pain; lack of responsiveness to drugs for organic movement disorders; and response to placebo drugs and suggestion.

A simple way to check for entrainment is to have the patient mimic a movement at a specific frequency. "If the patient has a tremor in the left hand at a certain frequency, we have them do rapid alternating finger tapping movements with their right hand at a given frequency, and often times we will see that the psychogenic tremor will assume the frequency of the voluntary movement," said Hinson. A good test for distractibility, she said, is to have the patient count backward from 100 in sevens and see if this affects his movements.

Jankovic reported that he will sometimes use the power of suggestion to check for a PMD. For example, he might tell a patient with intermittent tremor that vibration can trigger the tremor in some patients and then apply a tuning fork to the affected part of the body. "In most cases, the patient suddenly develops tremor, even though it's not due to any organic cause, but just to my suggestion." He said that a converse suggestion also could work: suggesting that the tuning fork will reduce the tremor.

"I have hundreds and hundreds of videotapes that show complete resolution of the tremor with the power of suggestion," he said. This strategy helps define the phenomenology and provides further support for the diagnosis.

Another test that can be used to aid in diagnosis is the administration of a placebo. Hinson recommended giving placebos in a double-blind fashion-and only with the patient's consent, to avoid feelings of deception or mistrust. She also cautioned that organic movement disorders may temporarily improve in response to placebo administration, so placebo response should not be used as the sole criterion for a diagnosis of a PMD.

Kompoliti agreed that neurologists need to be cautious with these diagnoses. For example, she pointed out that it is possible for more than 1 movement disorder-such as Parkinson and chorea-to coexistent in the same patient. Furthermore, certain movement disorders, such as dystonia, can be bizarre in their presentation and their triggers.

Neurologists may need to perform tests such as MRI or spinal fluid analysis to exclude organic causes of the symptoms. However, said Jankovic, these tests usually already have been performed by the time he sees a patient at his center. "I rely on examination," he said. "There's no blood test that can tell someone they have PMD."

Neurologists also can use tests such as EMG-based tremor analysis and EMG analysis of myoclonus to quantify movement disorders. "With an EMG, you can document this entrainment phenomenon much more specifically than you can just visually because you can show the frequency of the tremor, you can show exactly the changes of frequency of the tremor with distraction," said Hinson, who noted that she rarely uses this test.

European physicians sometimes use functional brain scans such as [

I]-CIT single-photon-emission CT and fluorodopa positron emission tomography scans to check for dopaminergic cell loss in the brain, but these are used primarily in research settings in the United States.

DIAGNOSIS DOMAIN Of NEURO MOVEMENT SPECIALIST


It is difficult for a neurologist who doesn't see a lot of patients with PMD to make a diagnosis, conceded Jankovic. "I would say that the vast majority of these patients-80% or 90%-had another diagnosis before they saw us," he said.

There is also a risk that someone with an organic movement disorder will be misdiagnosed with a PMD. "Before we disclose the diagnosis to the patient, we want to be 100% sure that this is a correct diagnosis and that we have excluded all organic causes," said Jankovic. This is why it is a good idea to refer patients with a suspected PMD to a movement disorder center.

The diagnosis should be made by a neurologist who specializes in movement disorders rather than by a psychiatrist or psychologist, emphasized Jankovic. He said that it is extremely frustrating to diagnose a PMD, send the patient to a psychologist or a psychiatrist for treatment, and have that specialist tell them they are psychologically "fine" and that their disease is organic-a surprisingly common occurrence.

Hinson agreed that a neurologist who specializes in movement disorders should be tasked with making the diagnosis of a PMD, but she pointed out that psychiatrists can help refine the diagnosis and identify whether the PMD is related to a conversion disorder, somatoform disorder, factitious disorder, or to malingering.

Hinson reported that neurologists often refer cases to her when they are uncertain about the diagnosis. Other times, the referring neurologist has made the diagnosis but the patient has refused to accept it. Finally, some neurologists shy away from making the diagnosis themselves because they fear that the patient will not be receptive to it.


How can neurologists get patients to accept a diagnosis of PMD?

"You need to deliver the diagnosis with a lot of sensitivity so that the patient trusts the doctor, does not feel rejected, and buys into the treatment process," said Hinson. The first step is to acknowledge that the patient has a movement disorder. "I say, for example, 'You have a tremor disorder. There's no doubt about that.'" Hinson then goes on to explain that there are different causes of tremor. "I say that there's parkinsonian tremor, there's essential tremor, there's drug-induced tremor, and there's psychogenic tremor."

She then goes through each of these causes and explains why the patient's disease either does or does not fit the criteria. "I say, your tremor does not fit into Parkinson's type tremor because of this and that, and patients can understand this . . . They think, 'my tremor is different.'"

Finally, she delivers her conclusion: "It's not Parkinson's, it's not essential tremor, it's not drug- induced; your tremor falls in the category of psychogenic tremor. So what does that mean?" She then explains to the patient that the emotion center in the brain is tightly linked with the motion center in the brain, and if there's an emotional disturbance, the body can react with motor symptoms.

"I often make the analogy that on a small scale, if someone who is supposed to speak in public is nervous, their hands might start shaking, or if they're embarrassed, their face might get red, so emotional feelings can translate into physical symptoms." She said that most patients are receptive to the analogy and understand what she is saying.

"Then I underline that the patient has a movement disorder but that the origin of the movement disorder is not cell death or neurodegenerative disease like in Parkinson's. I stress that the disorder is an abnormal function of the brain that is triggered by emotions."	

Hinson also emphasizes that the disease is curable and that the movements can go away because brain damage is not involved. She said that patients like hearing that brain damage is not an issue and that they can "get better."

Finally, Hinson tells them that the only way for them to improve is to follow through with treatment from a psychiatrist. "Because I tell them where I'm coming from and how I make the diagnosis, they're usually 'with' me [about the diagnosis and treatment recommendation] and will follow up with my psychiatric colleague."

Jankovic said that about 99% of his patients accept the diagnosis, but admitted that this wasn't always the case. "I'll be honest with you, when I first started seeing these patients, my success rate was much lower than that. I didn't know exactly how to approach them."

He agreed with Hinson that a sensitive delivery is essential. Too often, patients have the impression that the physician does not believe them and thinks the problem is "all in their head." "My feeling is that I have to convey to them that I do believe them, I do believe that what they're telling me bothers them, and that these symptoms are not entirely under their control."

Jankovic said that he emphasizes stress as the cause of the disorder and attempts to identify what type of stress might be at play. "I would say that in 80% or 90% of cases we can clearly identify what the stress factor might be at the time of the initial visit." He added that some patients will initially deny having stress as a precipitating factor but that further interviews with the patient, family members, and friends will generally reveal a specific stress trigger.

Kompoliti agreed that the diagnosis is difficult for patients to accept. She likes to emphasize the positive. "I tell them, 'this is the best news I could have given you today. If you had Parkinson disease, it would have been bad news: it's progressive, you have it for the rest of your life, and it could put you in a wheelchair, but you don't have that.'"

Her next step is to explain how important it is to act quickly to begin treatment because patients with recent-onset PMD have the best chance of getting better.


Treatment may involve sessions with a psychiatrist, a psychologist, or both. Hinson prefers to refer patients to a psychiatrist who has a special interest in somatoform disorders, but said any reputable psychiatrist would be suitable. If patients are recruiting their own mental health professional, Hinson requests that the patient have the psychiatrist call her. "The psychiatrist often needs reassurance from the neurologist that the condition is indeed psychogenic," she said.

The psychiatrist will devise a treatment plan that might include psychotherapy (either psychodynamic therapy or cognitive behavioral therapy); stress management and relaxation techniques such as biofeedback, yoga, and meditation; and medication for associated depression and anxiety. Many psychiatrists will refer the patient to a psychologist for the psychotherapy or stress management components. In addition, some patients may benefit from treatment by a physical or occupational therapist to reestablish normal motor function.

About half of Hinson's patients in whom a PMD diagnosis is made are requested to check back with Hinson after 3 months of once-weekly psychotherapy. "Some patients do well with the reassurance that someone is overseeing the treatment process," she said.

Jankovic's preference is to send patients directly to psychologists, especially those who specialize in stress management techniques such as biofeedback. He and his colleagues at Baylor have recently embarked on an independent review board-approved study of transcutaneous nerve stimulation as a means of "relaxing" the abnormally contracting muscles.


Few studies have looked at the long-term outcome of PMD. However, there is evidence that persons who are least likely to recover are those who are symptomatic for more than 6 months; those with insidious onset of PMD; and those with a primary psychiatric diagnosis of hypochondriasis, factitious disorder, or malingering.

In the largest longitudinal study to date (228 patients seen at the Baylor Movement Disorders Clinic), nearly 57% of patients improved, 22% worsened, and 21% remained the same after an average follow-up of 3.4 years. Patients who were most likely to recover were those in good physical health, with positive perceptions of their social life, who perceived that they were receiving effective treatment, who eliminated stressors in their life, and who were treated with a specific medication.

"We found that patients who initially accept their diagnosis do well," said Jankovic. Hinson agreed. "I think we can prevent a lot of harm by delivering the diagnosis quickly and precisely and not shying away from it," she said. "We can see very good success with the appropriate treatment."  

 Lees AJ. Odd and unusual movement disorders. 

 Factor SA, Podskalny GD, Molho ES. PMDs: frequency, clinical profile, and characteristics. 

 Jankovic J, Vuong KD, Thomas M. Psychogenic tremor: long-term outcome.

 Williams DT, Ford B, Fahn S. Phenomenology and psychopathology related to PMDs.

 Hinson VK, Cubo E, Comella CL, et al. Rating scale for PMDs: scale development and clinimetric testing.

 Ranawaya R, Riley D, Lang A. Psychogenic dyskinesias in patients with organic movement disorders. 

 Marsden CD. Hysteria-a neurologist's view. 

 Feinstein A, Stergiopoulos V, Fine J, Lang AE. Psychiatric outcome in patients with a PMD: a prospective study. 

Neuropsychiatry Neuropsychol Behav Neurol. 

 Thomas M, Vuong KD, Jankovic J. Long-term prognosis of patients with PMDs. 

Five words that are guaranteed to annoy your patientwith a diagnosis of psychogenic movementdisorder (PMD) are It's all in your head.It's the worst thing you can say, said Katie Kompoliti,MD, associate professor of neurological sciencesat Rush University Medical Center in Chicago.

Clinical Pearls on Best Approaches to Psychogenic Movement Disorders

The greatest advance in reducing mortality from bacterial meningitis over the past 20 years has been the advent of widespread immunization. Vaccination has also had another effect: changing which forms of the disease are most prevalent.

"Vaccination is the main factor that has changed the epidemiology of bacterial meningitis in the United States," said Allan R. Tunkel, MD, PhD, the lead author of practice guidelines for bacterial meningitis from the Infectious Diseases Society of America (IDSA). Tunkel is also chair of the Department of Medicine at Monmouth Medical Center in Long Branch, New Jersey.

Most bacterial meningitis was once caused by 

, but with widespread childhood immunization against 

 type b (Hib) in the developed world starting in the early 1990s, Hib infection has become rare; 

 have emerged as the leading causes of bacterial meningitis.

Another relatively recent change in bacterial meningitis has been decreased susceptibility of meningitis-causing bacteria-especially 

-to antimicrobial agents. Tunkel explained that in the 1970s in the United States "virtually all pneumococci were exquisitely sensitive to penicillin, but what we've seen over recent years is that pneumococci have become either intermediately susceptible or highly resistant to penicillin."

The emergence of antibiotic-resistant strains has changed the way bacterial meningitis is treated, causing physicians to routinely use vancomycin in combination with a third-generation cephalosporin as empiric therapy for presumed pneumococcal meningitis.

Devon Schuyler

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