Thalamic syndrome
Encyclopedia
Dejerine–Roussy syndrome or thalamic pain syndrome is a condition developed after a thalamic stroke
, a stroke causing damage to the thalamus. This condition is not to be confused with "Roussy-Levy Syndrome", a genetic disorder. 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
. 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".
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 occurring in the brain. 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.
. Less commonly, some patients develop severe ongoing pain with little or no stimuli.
Allodynia
refers to hypersensitivity to sensations associated with a stimulus that would normally not cause pain. 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.
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.
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.
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. Although debatable, these symptoms are rare and considered part of a "thalamic phenomenon", and are not normally considered a characteristic of Dejerine–Roussy syndrome.
. The thalamus is the part of the brain responsible for sensation and emotion. 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. 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 infantile, these findings hold promise for an objective way to understand and treat patients with Dejerine–Roussy syndrome.
. The right and left hemispheres of the brain both play important roles in the sensory input and output. 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.
Due to the uniqueness of each case, a close clinician-patient relationship is vital in diagnosis and treatment. Stroke rehabilitation clinic staff debriefs the patient, then reviews information from the initial stroke to determine the location of brain lesioning. Some may attempt to correlate lesions with the type and severity of pain in order to prescribe the best treatment option and coping strategies. Hypersensitivity in conjunction with lesions within the thalamus allow for the diagnosis of Dejerine–Roussy syndrome. A typical stroke rehabilitation clinic may have between 10 and 15 Dejerine–Roussy patients at a time, each with differing symptoms from each other. Cases diagnosed and treated are primarily moderate to severe cases of Dejerine Roussy syndrome, and mild cases usually go undiagnosed.
including Dejerine–Roussy syndrome. Symptoms are generally not treatable with ordinary analgesics. 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.
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.
Stroke
A stroke, previously known medically as a cerebrovascular accident , is the rapidly developing loss of brain function due to disturbance in the blood supply to the brain. This can be due to ischemia caused by blockage , or a hemorrhage...
, a stroke causing damage to the thalamus. This condition is not to be confused with "Roussy-Levy Syndrome", a genetic disorder. 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
Allodynia
Allodynia is a pain due to a stimulus which does not normally provoke pain. Temperature or physical stimuli can provoke allodynia, and it often occurs after injury to a site...
. 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".
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".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".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 occurring in the brain. 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.
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. The majority of those reported are cases in which the symptoms are severe and debilitating. Burning and tingling can also be accompanied by hypersensitivity, usually in the form of dysaesthesia or allodyniaAllodynia
Allodynia is a pain due to a stimulus which does not normally provoke pain. Temperature or physical stimuli can provoke allodynia, and it often occurs after injury to a site...
. Less commonly, some patients develop severe ongoing pain with little or no stimuli.
Allodynia
Allodynia
Allodynia is a pain due to a stimulus which does not normally provoke pain. Temperature or physical stimuli can provoke allodynia, and it often occurs after injury to a site...
refers to hypersensitivity to sensations associated with a stimulus that would normally not cause pain. 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.
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.
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.
Pain associated with Dejerine–Roussy syndrome is sometimes coupled with anosognosia
Anosognosia
Anosognosia /æˌnɒsɒgˈnəʊsɪə/ is a condition in which a person who suffers disability seems unaware of the existence of his or her disability. Unlike denial, which is a defense mechanism, anosognosia is rooted in physiology...
or somatoparaphrenia
Somatoparaphrenia
Somatoparaphrenia is a type of monothematic delusion where one denies ownership of a limb or an entire side of one's body. As an example, a patient would believe that her or his own arm would belong to the doctor, or that another patient left it behind....
which causes a patient having undergone a right-parietal, or right-sided stroke to deny any paralysis
Paralysis
Paralysis is loss of muscle function for one or more muscles. Paralysis can be accompanied by a loss of feeling in the affected area if there is sensory damage as well as motor. A study conducted by the Christopher & Dana Reeve Foundation, suggests that about 1 in 50 people have been diagnosed...
of the left side when indeed there is, or deny the paralyzed limb(s) belong to them. Although debatable, these symptoms are rare and considered part of a "thalamic phenomenon", and are not normally considered a characteristic of Dejerine–Roussy syndrome.
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 thalamusThalamus
The thalamus is a midline paired symmetrical structure within the brains of vertebrates, including humans. It is situated between the cerebral cortex and midbrain, both in terms of location and neurological connections...
. The thalamus is the part of the brain responsible for sensation and emotion. 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
Afferent
Afferent is an anatomical term with the following meanings:*Conveying towards a center, for example the afferent arterioles conveying blood towards the Bowman's capsule in the Kidney. Opposite to Efferent.*Something that so conducts, see Afferent nerve fiber...
pathway and the cortex of the brain, changing what one feels. 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
Brain mapping
Brain mapping is a set of neuroscience techniques predicated on the mapping of quantities or properties onto spatial representations of the brain resulting in maps.- Overview :...
.
Recently, magnetic resonance imaging
Magnetic resonance imaging
Magnetic resonance imaging , nuclear magnetic resonance imaging , or magnetic resonance tomography is a medical imaging technique used in radiology to visualize detailed internal structures...
has been utilized to correlate lesion size and location with area affected and severity of condition. Although infantile, these findings hold promise for an objective way to understand and treat patients with Dejerine–Roussy syndrome.
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 plasticityPlasticity
Plasticity may refer to:Science* Plasticity , in physics and engineering, plasticity is the propensity of a material to undergo permanent deformation under load...
. The right and left hemispheres of the brain both play important roles in the sensory input and output. 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
Anosognosia
Anosognosia /æˌnɒsɒgˈnəʊsɪə/ is a condition in which a person who suffers disability seems unaware of the existence of his or her disability. Unlike denial, which is a defense mechanism, anosognosia is rooted in physiology...
and somatoparaphrenia
Somatoparaphrenia
Somatoparaphrenia is a type of monothematic delusion where one denies ownership of a limb or an entire side of one's body. As an example, a patient would believe that her or his own arm would belong to the doctor, or that another patient left it behind....
).
The insular cortex
Insular cortex
In each hemisphere of the mammalian brain the insular cortex is a portion of the cerebral cortex folded deep within the lateral sulcus between the temporal lobe and the frontal lobe. The cortical area overlying it towards the lateral surface of the brain is the operculum...
, part of the cerebral cortex
Cerebral cortex
The cerebral cortex is a sheet of neural tissue that is outermost to the cerebrum of the mammalian brain. It plays a key role in memory, attention, perceptual awareness, thought, language, and consciousness. It is constituted of up to six horizontal layers, each of which has a different...
, is responsible for self-sensation, including the degree of pain perceived by the body, and for self-awareness
Self-awareness
Self-awareness is the capacity for introspection and the ability to reconcile oneself as an individual separate from the environment and other individuals...
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.Due to the uniqueness of each case, a close clinician-patient relationship is vital in diagnosis and treatment. Stroke rehabilitation clinic staff debriefs the patient, then reviews information from the initial stroke to determine the location of brain lesioning. Some may attempt to correlate lesions with the type and severity of pain in order to prescribe the best treatment option and coping strategies. Hypersensitivity in conjunction with lesions within the thalamus allow for the diagnosis of Dejerine–Roussy syndrome. A typical stroke rehabilitation clinic may have between 10 and 15 Dejerine–Roussy patients at a time, each with differing symptoms from each other. Cases diagnosed and treated are primarily moderate to severe cases of Dejerine Roussy syndrome, and mild cases usually go undiagnosed.
Treatments
Many chemical medications have been used for a broad range of neuropathic painNeuropathic pain
Neuropathic pain results from lesions or diseases affecting the somatosensory system. It may be associated with abnormal sensations called dysesthesia, which occur spontaneously and allodynia that occurs in response to external stimuli. Neuropathic pain may have continuous and/or episodic ...
including Dejerine–Roussy syndrome. Symptoms are generally not treatable with ordinary analgesics. 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
Brain
The brain is the center of the nervous system in all vertebrate and most invertebrate animals—only a few primitive invertebrates such as sponges, jellyfish, sea squirts and starfishes do not have one. It is located in the head, usually close to primary sensory apparatus such as vision, hearing,...
and spinal cord
Spinal cord
The spinal cord is a long, thin, tubular bundle of nervous tissue and support cells that extends from the brain . The brain and spinal cord together make up the central nervous system...
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.
Pharmaceutical treatment
- Opiates contain the narcotics morphineMorphineMorphine is a potent opiate analgesic medication and is considered to be the prototypical opioid. It was first isolated in 1804 by Friedrich Sertürner, first distributed by same in 1817, and first commercially sold by Merck in 1827, which at the time was a single small chemists' shop. It was more...
, codeineCodeineCodeine or 3-methylmorphine is an opiate used for its analgesic, antitussive, and antidiarrheal properties...
, and papaverinePapaverinePapaverine is an opium alkaloid antispasmodic drug, used primarily in the treatment of visceral spasm, vasospasm , and occasionally in the treatment of erectile dysfunction...
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. 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.
- 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 serotoninSerotoninSerotonin or 5-hydroxytryptamine is a monoamine neurotransmitter. Biochemically derived from tryptophan, serotonin is primarily found in the gastrointestinal tract, platelets, and in the central nervous system of animals including humans...
reuptake inhibitors have been used to treat this symptom and they are effective to some degree within a short time window.
- Anti-convulsants reduce neuronal hyperexcitability, effectively targeting Dejerine–Roussy syndrome. GabapentinGabapentinGabapentin is a pharmaceutical drug, specifically a GABA analogue. It was originally developed for the treatment of epilepsy, and currently is also used to relieve neuropathic pain...
and pregabalinPregabalinPregabalin is an anticonvulsant drug used for neuropathic pain and as an adjunct therapy for partial seizures with or without secondary generalization in adults. It has also been found effective for generalized anxiety disorder and is approved for this use in the European Union. It was designed...
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.
- Topical treatment such as lidocaineLidocaineLidocaine , Xylocaine, or lignocaine is a common local anesthetic and antiarrhythmic drug. Lidocaine is used topically to relieve itching, burning and pain from skin inflammations, injected as a dental anesthetic or as a local anesthetic for minor surgery.- History :Lidocaine, the first amino...
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.
- 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 treatment lasted ~10 days, a comparatively longer refractory period than any of the traditional pharmaceutical treatments.
Stimulation treatments
- Electrode stimulation from surgically implanted electrodes has been studied in the past decade in hopes of a permanent pain treatment without refraction. Electric stimulation utilizing implants most often use different dosages of radiationRadiationIn physics, radiation is a process in which energetic particles or energetic waves travel through a medium or space. There are two distinct types of radiation; ionizing and non-ionizing...
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.
- 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 received initial 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.
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 insulaInsulaInsula is the Latin word for "island" and may refer to:*Insular cortex, a human brain structure*Insula , an apartment building in ancient Rome that provided housing for all but the elite...
. 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 plasticityPlasticityPlasticity may refer to:Science* Plasticity , in physics and engineering, plasticity is the propensity of a material to undergo permanent deformation under load...
of the brain, Ramachandran and associates were able to accept their hypothesis with significant data proving cold vestibularVestibularThe Vestibular is a competitive examination and is the primary and widespread system used by Brazilian universities to select their students. The Vestibular usually takes place from November to January, right before the start of school year in February or March, although certain universities hold...
caloric stimulation can treat Dejerine–Roussy syndrome. Although cold water titrated down the ear canal may cause extreme discomfort for a short amount of time, caloric stimulation offers a non-invasive option for possible treatment of Dejerine–Roussy syndrome.
Demographics
Of the millions experiencing strokes worldwide, over 30,000 in the United States alone have developed some form of Dejerine–Roussy syndrome. 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.See also
- Central post-stroke pain
- StrokeStrokeA stroke, previously known medically as a cerebrovascular accident , is the rapidly developing loss of brain function due to disturbance in the blood supply to the brain. This can be due to ischemia caused by blockage , or a hemorrhage...
- Neuropathic painNeuropathic painNeuropathic pain results from lesions or diseases affecting the somatosensory system. It may be associated with abnormal sensations called dysesthesia, which occur spontaneously and allodynia that occurs in response to external stimuli. Neuropathic pain may have continuous and/or episodic ...
- Central pain syndromeCentral pain syndromeCentral pain syndrome is a neurological condition caused by damage or malfunction in the Central Nervous System which causes a sensitization of the pain system. The extent of pain and the areas affected are related to the cause of the injury, which can include trauma, tumors, stroke, Multiple...
- Thalamic pain syndrome
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