Dejerine-Roussy (Thalamic) Syndrome

Dejerine-Roussy syndrome or thalamic pain syndrome is a condition developed after a thalamic stroke, a stroke causing damage to the thalamus. ^[1], ^[2]. This condition is not to be confused with "Roussy-Levy Syndrome", a genetic disorder ^[3], ^[4], ^[5]. Ischemic strokes and Hemorrhagic strokes can cause lesioning in the thalamus. The lesions, usually present in one hemisphere of the brain most often cause an initial lack of sensation and tingling in the opposite side of the body. Weeks to months later, numbness can develop into severe and chronic pain that is not proportional to an environmental stimulus, called dysaesthesia or allodynia ^[1]. As initial stroke symptoms: numbness and tingling, dissipate, an imbalance in sensation causes these later syndromes, characterizing Dejerine-Roussy syndrome. Although some treatments exist, they are often expensive, chemically-based, invasive, and only treat patients for some time before they need more treatment, called "refractory treatment" ^[2].

Eponym

Dejerine-Roussy syndrome has also been referred to as: "Posterior Thalamic Syndrome", "Retrolenticular Syndrome", "Thalamic Hyperesthetic Anesthesia", "Thalamic Pain Syndrome", "Thalamic Syndrome", "Central Pain Syndrome", and "Central Post-Stroke Syndrome" ^[2], ^[6], ^[7].

Symptoms

Dejerine-Roussy syndrome is most commonly preceded by numbness in the affected side. In these cases, numbness is replaced by burning and tingling sensations, widely varying in degree of severity across all cases ^[8]. The majority of those reported are cases in which the symptoms are severe and debilitating ^[9]. Burning and tingling can also be accompanied by hypersensitivity, usually in the form of dysaesthesia or allodynia. Less commonly, some patients develop severe ongoing pain with little or no stimuli ^[10].

Allodynia refers to hypersensitivity to sensations associated with a stimulus that would normally not cause pain ^[1], ^[11], ^[12]. For example, there is a patient in the Emory Stroke Program who currently cowers to unrelenting pain when a breeze touches his skin. Most patients experiencing allodynia, experience pain with touch and pressure, however some can be hypersensitive to temperature ^[9]. Dysaesthesia is defined as pain due to thalamic lesioning. This form of neuropathic pain can be any combination of itching, tingling, burning, or searing experienced spontaneously or from stimuli ^[12].

Allodynia and dysaesthesia replace numbness between one week and a few months after a thalamic stroke. In general, once the development of pain has stopped, the type and severity of pain will be unchanging and if untreated, persist throughout life. Consequentially, many will undergo some form of pain treatment and adjust to their new lives as best they can ^[9].

Pain associated with Dejerine-Roussy syndrome is sometimes coupled with anosognosia or somatoparaphrenia which causes a patient having undergone a right-parietal, or right-sided stroke to deny any paralysis of the left side when indeed there is, or deny the paralyzed limb(s) belong to them^[1]. Although debatable, these symptoms are rare and considered part of a "thalamic phenomenon", and are not normally considered a characteristic of Dejerine-Roussy syndrome ^[9].

Causes and Pathophysiology

Although there are many contributing factors and risks associated with strokes, there are very few associated with Dejerine-Roussy syndrome and thalamic lesions specifically. In general, strokes damage one hemisphere of the brain, which can include the thalamus. The thalamus is the part of the brain responsible for sensation and emotion ^[11]. It is known that sensory information from environmental stimuli travels to the thalamus for processing and then to the somatosensory cortex for interpretation. The final product of this communication is the ability to feel a pressure or temperature as interpreted by the brain. The damage in the thalamus causes miscommunication between the afferent pathway and the cortex of the brain, changing what one feels ^[2]. The change could be an incorrect sensation experienced, or inappropriate amplification or dulling of a sensation. Because the brain is considered plastic and each individual's brain is different, it is almost impossible to know how a sensation will be changed without brain mapping.

Recently, magnetic resonance imaging has been utilized to correlate lesion size and location with area affected and severity of condition. Although infnatile, these findings hold promise for an objective way to understand and treat patients with Dejerine-Roussy syndrome ^[13]. Research in the last few years has proposed a mechanism of action for characterization of Dejerine-Roussy syndrome, as described below.

Proposed Mechanism

The imbalance in sensation characterized by Dejerine-Roussy syndrome can be argued through a model addressing a system of inputs and outputs that the brain must constantly process throughout life, suggesting latent plasticity The right and left hemispheres of the brain both play important roles in the sensory input and output^[1]. When a stroke damages one hemisphere, it is proposed that the other hemisphere will cope with the discrepancies in a specific manner. The left hemisphere tends to “gloss over” discrepancies from inputs, eliciting either denial or rationalization defense mechanisms in order to stabilize said discrepancy. In contrast, the right hemisphere does the opposite, and will focus on the discrepancy, and motivate action to be taken to restore equilibrium. Therefore, damage to the left hemisphere can cause both an indifference to pain and hypersensitivity to pain (dysaesthesia or alloydnia), while damage to the right hemisphere can cause denial as a defense mechanism (anosognosia and somatoparaphrenia). The insular cortex, part of the cerebral cortex, is responsible for self-sensation, including the degree of pain perceived by the body, and for self-awareness and defense mechanisms. The insular cortex is often lesioned by a stroke. Particularly, the posterior insula has been mapped to correlate to pain experienced by an individual. In addition, is has been proven that the posterior insula receives a substantial amount of the inputs of the brain, and can be treated with visual, kinesthetic, and auditory inputs.

Diagnosis

Individuals with emerging Dejerine-Roussy syndrome usually report they are experiencing unusual pain or sensitivity, and should visit a post-stroke rehabilitation center immediately. Stroke rehabilitation clinics are located worldwide and specialize in diagnosis, prognosis, and treatment of conditions associated post-stroke ^[9]. Go to See Also and External Links for information on finding a stroke clinic near you.

Due to the uniqueness of each case, a close clinician-patient relationship is vital in diagnosis and treatment. Stroke rehabilitation clinic staff debrief the patient, then review information from the initial stroke to determine the location of brain lesioning ^[9]. As mentioned earlier, some may attempt to correlate lesions with the type and severity of pain in order to prescribe the best treatment option ^[13] and coping strategies. Hypersensitivity in conjunction with lesions within the thalamus allow for the diagnosis of Dejerine-Roussy syndrome ^[2]. A typical stroke rehabiliation clinic may have between 10 and 15 Dejerine-Roussy patients at a time, each with differing symptoms from eachother. Cases diagnosed and treated are primarily moderate to severe cases of Dejerine Roussy syndrome, and mild cases usually go undiagnosed ^[12].

Treatments

Many chemical medications have been used for a broad range of neuropathic pain including Dejerine-Roussy syndrome. Symptoms are generally not treatable with ordinary analgesics ^[14]. Traditional chemicals include opiates and anti-depressants. Newer pharmaceuticals include anti-convulsants and Kampo medicine. Pain treatments are most commonly administered via oral medication or periodic injections. Topical In addition, physical therapy has traditionally been used alongside a medication regimen. More recently, electrical stimulation of the brain and spinal cord and caloric stimulation have been explored as treatments.

The most common treatment plans involve a schedule of physical therapy with a medication regimen. Because the pain is mostly unchanging after development, many patients test different medications and eventually choose the regimen that best adapts to their lifestyle, the most common of which are anti-depressants and pain injections ^[9].

Pharmaceutical Treatment

• Opiates contain the narcotics morphine, codeine, and papaverine which provide pain relief. Opiates activate opiate receptors in the brain which alter the brain's perception of sensory input, alleviating pain and sometimes inducing pleasure for a short time period. When intravenously administered, opiates can relieve neuropathic pain but only for a time between 4 and 24 hours. After this time window, the pain returns and the patient must be treated again ^[2], ^[9]. Although this method of treatment has been proven to reduce pain, the repetitive use of opiates has also been linked to the activation of the brain's reward system and therefore poses a threat of addiction. The potential destruction opiates can cause have drawn many doctors and patients away from their use ^[9].

• Anti-depressants are traditionally administered for treatment of mood disorders, also linked to the thalamus, and can be used to treat Dejerine-Roussy symptoms. Specifically tricyclic anti-depressants such as Amytriptyline and selective serotonin reuptake inhibitors have been used to treat this symptom and they are effective to some degree within a short time window ^[2], ^[14].

• Anti-convulsants reduce neuronal hyperexcitability, effectively targeting Dejerine-Roussy syndrome. Gabapentin and pregabalin are the most common anti-convulsants. They have significant efficacy in treatment of peripheral and central neuropathic pain. Treatments last 4-12 hours and in general are well tolerated, and the occurrence of adverse events does not differ significantly across patients. Commonly reported side-effects are dizziness, decreased intellectual performance, somnolence, and nausea ^[2].

• Topical treatment such as lidocaine patches can be used to treat pain locally. The chemical is released to the skin to act as a numbing agent that feels cool, then feels warm, much like IcyHot ^[9].

• Kampo medicine has been research in a case study to test the efficacy of a medicine called Sokeikakketsuto decoction in Dejerine-Roussy pain symptoms. The patients studied did not respond to antidepressants and antiepileptic drugs, and turned to Kampo medicine as a treatment option. Pain experienced by patients significantly decreased and some had improved dysesthesia. The mechanism of action blocking pain is currently unknown. The effects of this treament lasted ~10 days, a comparatively longer refractory period than any of the traditional pharmaceutical treatments ^[14].

Stimulation Treatments

• Electrode stimulation from surgically implanted electrodes has been studied in the past decade in hopes of a permenent pain treatment without refraction. Electric stimulation utilizing implants most often use different dosages of radiation delivered to a specific part of the brain. Many studies have concluded initial efficacy in such implants, but pain often re appears after a year or so ^[15].

• Spinal cord stimulation has been studied in the last couple of years. In a long case study, 8 patients were given spinal cord stimulation via insertion of a percutaneous lead at the appropriate level of the cervical or thoracic spine. Between 36 and 149 months after the stimulations, the patients were interviewed. 6 of the 8 had recieved intial pain relief, and three experiences long-term pain relief. Spinal cord stimulation is cheaper than brain stimulation and less invasive, and is thus a more promising option for pain treatment ^[16].

Expensive and invasive, the above treatments are not guaranteed to work, and are not meeting the needs of patients. There is a need for a new, less expensive, less invasive form of treatment, one of which is postulated below.

• In 2007, Dr. V. S. Ramachandran and his lab proposed a new method, simple and completely non-invasive for treating those affected with Dejerine-Roussy syndrome. Caloric stimulation of the ear opposite the affected side of the brain has been proven to activate the posterior insula. Consequentially, Ramachandran and associates explored a new non-invasive method of treating the symptoms of Dejerine-Roussy syndrome through caloric stimulation via water through the auditory canal. They hypothesized that if cold water was streamed into the ear down the auditory canal, the symptoms associated with Dejerine-Roussy syndrome would be alleviated. The experiment conducted utilized two stroke patients with hypersensitivity to pain decades after having a stroke. Both patients had immediate and nearly complete relief in the face and arms, and some relief in the legs. In addition to further proving latent plasticity of the brain, Ramachandran and associates were able to accept their hypothesis with significant data proving cold vestibular caloric stimulation can treat Dejerine-Roussy syndrome. Although cold water titrated down the ear canal may cause extremem discomfort for a short amount of time, caloric stimulation offers a non-invasive option for possible treatment of Dejerine-Roussy syndrome ^[1].

Demographics

Of the millions experiencing strokes worldwide, over 30,000 in the United States alone have developed some form of Dejerine-Roussy syndrome ^[1]. 8% of all stroke patients will experience central pain syndrome, with 5% experiencing moderate to severe pain. The risk of developing Dejerine-Roussy syndrome is higher in older stroke patients, about 11% of stroke patients over the age of 80 ^[2].

History

In 1906, Joseph Jules Déjerine and Gustave Roussy provided descriptions of central post-stroke pain (CPSP) in their paper entitled: "Le syndrome thalamique”. The name Dejerine-Roussy syndrome was coined after their deaths. The syndrome included “…severe, persistent, paroxysmal, often intolerable, pains on the hemiplegic side, not yielding to any analgesic treatment” ^[2]. In 1911, it was found that that the patients often developed pain and hypersensitivity to stimuli during recovery of function. And thus is was thought that the pain associated after stroke was part of the stroke and lesion repair process occuring in the brain ^[9]. It is now accepted that Dejerine-Roussy syndrome is a condition developed due to lesions interfering with the sensory process, which triggered the start of anti-depressant and brain stimulation research. The last 50 years have been filled with refractory treatment research. As of the early 2000's, longer treatments lasting months to years have been explored in the continued search for permanent removal of abnormal pain ^[9], ^[2].

See Also

Central post-stroke pain

Stroke

Neuropathic pain

Central pain syndrome

Thalamic pain syndrome

References

1. ^ ^{a b c d e f g} Ramachandran, V. S., McGeoch, P. D., & Williams, L. (2007). Can vestibular caloric stimulation be used to treat Dejerine-Roussy Syndrome? Med Hypotheses, 69(3), 486-488. doi: 10.1016/j.mehy.2006.12.036
2. ^ ^{a b c d e f g h i j k} Klit, H., Finnerup, N. B., Jensen, T. S. (2009). Central post-stroke pain: clinical characteristics, pathophysiology, and management. Lancet Neurol. 8, 857-868.
3. ^ Auer-Grumbach, M., Strasser-Fuchs, S., Wagner, K., Korner, E., Fazekas, F. (1998). Roussy–Le´vy syndrome is a phenotypic variant of Charcot–Marie–Tooth syndrome IA associated with a duplication on chromosome 17p11.2. Journal of Neurological Sciences, 154, 72-75.
4. ^ Haubrich, C., Krings, T., Senderek, J., Zuchner, S., Schroder, J. M., Noth, J., Topper, R. (2002). Hypertrophic nerve roots in a case of Roussy-Levy syndrome. Neuroradiology. 44, 933-937. doi: 10.1007/s00234-002-0847-2.
5. ^ Zubair, S., Holland, N. R., Beson, B., Parke, J. T., Prodan, C. I. (2008). A novel point mutation in the PMP22 gene in a family with Roussy-Levy syndrome. J Neurol. 255, 1417–1418. doi:10.1007/s00415-008-0896-5.
6. ^ (2011). Pain: Hope Through Research. National Institute of Neurological Disorders and Stroke. http://www.ninds.nih.gov/disorders/chronic_pain/detail_chronic_pain.htm.
7. ^ (2003). Thalamic Syndrome (Dejerine Roussy). National Organization for Rare Diseases. http://www.rarediseases.org/rare-disease-information/rare-diseases/byID/796/viewAbstract
8. ^ Hadley, R. (2004). Dejerine-Roussy Syndrome. Clinical Chiropractic. 7, 79-83. doi: 10.1016/j.clch.2003.11.003.
9. ^ ^{a b c d e f g h i j k l} Nahab, F. Emory University Stroke Program. Personal Interview with E. Tyburski. 7 October 2011.
10. ^ Wang, G., Thompson, (2008). S. M. Maladaptive Homeostatic Plasticity in a Rodent Model of Central Pain Syndrome: Thalamic Hyperexcitability after Spinothalamic Tract Lesions. J Neuroscience. 28(46), 11959 –11969. doi:10.1523/JNEUROSCI.3296-08.2008.
11. ^ ^{a b} Quiton, R. L., Masri, R., Thompson S. M., Keller, A. (2010). Abnormal Activity of Primary Somatosensory Cortex in Central Pain Syndrome. J Neurophysiol. 104, 1717-1725. doi:10.1152/jn.00161.2010
12. ^ ^{a b c} Bowsher, D. (2005). Allodynia in Relation to Lesion Site in Central Post-Stroke Pain. Jounral of Pain. 6(11), 736-740. doi:10.1016/j.jpain.2005.06.009.
13. ^ ^{a b} Misra, U. K., Kalita, J., Kumar, B. (2008). A Study of Clinical, Magnetic Resonance Imaging, and Somatosensory-Evoked Potential in Central Post-Stroke Pain. The Journal of Pain. 9(12), 1116-1122.
14. ^ ^{a b c}
15. ^ Hayashi, M., Chernov, M. F., Taira, T., Ochiai, T., Nakaya, K., Tamura, N., Goto, S., Yomo, S., Kouyama, N., Katayama, Y. Kawakami, Y., Izawa, M., Muragaki, Y., Nakamura, R., Iseki, H., Hori, T., Takakura, K. (2007). Outcome After Pituitary Radiosurgery for Thalamic Pain Syndrome. Int. J. Radiation Oncology Biol. Phys. 69(3), 852-857.
16. ^ Lopez, J. A., Torres, L. M., Gala, F., Iglesias, I. (2009). Spinal Cord Stimulation and Thalamic Pain: Long-term Results of Eight Cases. Neuromodulation. 12(3), 240-243.

External Links

http://www.stroke.org/site/PageServer?pagename=RESOUR

http://www.emoryhealthcare.org/rehabilitation-medicine/services/stroke.html

http://www.clinicaltrials.gov/ct2/results?term=dejerine+roussy+syndrome