Abstract
In the early 1900s Dejerine and Roussy first described with pathologic correlation a syndrome of severe unilateral pain following a lesion to the thalamus. Recognition that this syndrome can arise from lesions along the spinothalamic axis led to it being renamed central post-stroke pain (CPSP). Cardinal symptoms of CPSP include temperature and vibration sensitivity and hyperesthesia, dysesthesia, and allodynia. Aside from mild pain relief from amitriptyline, lamotrigine, and gabapentin, no treatment (medicinal or otherwise) has yet been shown to be beneficial in CPSP.
Definition
Central post-stroke pain (CPSP), formerly known as thalamic pain syndrome, is a chronic complex disabling pain syndrome characterized by pain and temperature sensation abnormalities after a cerebrovascular accident, infarct, or hemorrhage. It was first described, with pathophysiologic correlation to a lesion in the thalamus, in 1906 by Dejerine and Roussy as a “severe persistent, paroxysmal, often intolerant pain on the hemiplegic side, not yielding to analgesic treatment.” There were previous descriptions of pain after a central lesion by Edinger and others earlier in the 19th century.
The disease affects up to 8% to 12% of patients with stroke, in one study, 9% of hemorrhagic stroke patients with thalamic lesions. The prevalence of CPSP is particularly high: 25%, in those with Wallenberg lateral medullary syndrome. Pain onset in stroke patients occurs weeks to months after a cerebrovascular accident. CPSP is considered a persistent central neuropathic pain that follows an ischemic or hemorrhagic stroke without a peripheral cause. Although the pathogenesis remains unclear, there appears to be involvement not only of the thalamus as initially studied by Dejerine but can result from a lesion anywhere along the spinothalamic pathway causing the pain and temperature sensitivity. As a result, the term “thalamic pain” was replaced with “central post-stroke pain.” Interestingly, not all patients with lesions along the spinothalamic pathway have CPSP. Many CPSP patients have many lesions noted on magnetic resonance imaging that are unrelated to the pain.
Predictors as to those at risk are unclear, but in one study controls with thalamic stroke without thalamic pain had lesions mainly in the more anterolateral nuclei and patients with CPSP were noted to have lesions mainly in lateral and posterior thalamic nuclei on magnetic resonance imaging.
Symptoms
CPSP is characterized by mild hemiplegia, hemihypoesthesia, hyperpathia with burning sensation, hemiataxia, astereognosis, dyskinesias (especially choreoathetosis), and positive or negative pain sensations that occur for hours to continuously in the entire half the body, arm, leg, foot, or hand. Patients describe pain sensations as burning, cold, stabbing, sharp, aching, pricking, squeezing, shooting, tingling, or heavy when they are exposed to changes in temperature measured by a thermal probe, monofilament for tactile stimuli, and brushing with a stiff brush typically used for oil painting. Particularly excruciating are the sensory abnormalities, especially the thermal sensations that can include burning, scalding, or burning and freezing in addition to other vague descriptions of positive and negative sensory abnormalities. Symptoms can be constant or intermittent, described as burning by some CPSP patients, and triggered by touching of an item, being touched, or changes in temperature. Although symptoms usually begin within the first 6 months, symptoms can develop up to 10 years after the stroke. There can be wide fluctuations in pain intensity even on a daily basis, but movement, touch, temperature, or emotional stress can exacerbate the underlying pain. Because of the variable onset and symptom constellation, patients are often misdiagnosed.
Physical Examination
It is important in considering the diagnosis of CPSP to perform a thorough musculoskeletal and neurologic physical examination to rule out other causes of pain. Physical findings in patients with CPSP may include mild or more severe hemiplegia, hyperesthesia, or hypoesthesia. Patients may have impaired pinprick, temperature, and touch sensation, whereas vibration and joint proprioception are less commonly affected.
In a prospective study of 207 stroke patients, 87 subjects (16 with CPSP and 71 with no pain) with abnormal sensation were observed. The CPSP group was noted to have more abnormal sensibility to cold and warm stimuli compared with non–pain subjects with abnormal sensation. The 16 CPSP patients had evoked dysesthesia or allodynia (sensation of pain by stimuli that are usually nonpainful).
Functional Limitations
Strokes that cause CPSP are typically associated with only mild hemiplegia, although some patients can have moderate or severe hemiplegia and the functional limitations that accompany these. The pain of CPSP can often be a much more severe cause of functional limitation, at times to the point of being incapacitating.
Diagnostic Studies
Brain imaging of patients with CPSP will typically show a lesion in the spinothalamic pathway, but not all patients with such lesions will have CPSP.
Peripheral neuropathy
Traumatic brain injury
Syringomyelia
Multiple sclerosis
Complex regional pain syndrome
Shoulder disease (frozen shoulder, rotator cuff disease)
Deep venous thrombosis
Treatment
Initial
Historically, CPSP has been resistant to both medical and surgical management. Despite the severe impact on quality of life for patients with CPSP, there is limited scientific evidence of its treatment.
Temperature and vibration sensitivity were recognized as cardinal symptoms of CPSP from the initial report. Touch can cause severe hyperesthesia, dysesthesia, or allodynia. Thus measures must be taken to control these to prevent severe exacerbations of pain. These should include room heating or cooling and clothing use (as tolerated) so that the temperature is optimal for pain control. Patients have reported that riding in car, especially in traffic, can be excruciatingly painful due to vibration or even a light wind falling on the skin.
The only medications that have shown pain reduction in a randomized controlled trial are amitriptyline (75 mg daily), lamotrigine (200 mg daily), and gabapentin. Thus these medicines are considered first line management for CPSP. Unfortunately, even with these medicines, only mild pain relief was achieved, and many patients did not respond at all. Other medicines that have been found to have some benefit in open trials, such as nortriptyline, desipramine, imipramine, doxepin, venlafaxine, maprotiline, gabapentin, pregabalin, carbamazepine, mexiletine, fluvoxamine, and phenytoin, are considered second line treatment. In a randomized blinded parallel group placebo-controlled study, there was no statistical difference in the efficacy of the pregabalin 150 to 600 mg a day compared with the placebo regarding change in pain ratings, but there was a statistically significant improvement in sleep and anxiety. Studies suggest that selective serotonin reuptake inhibitors are ineffective treatment for CPSP.
For patients resistant to treatment, opioids (such as levorphanol, studied in a double-blind randomized controlled study) have been used, resulting in some pain reduction in a small group but not in a large population. In one study, intravenous morphine showed a modest short-term benefit in some patients. Long-term benzodiazepines are not recommended because of potentiation of inhibitory effects of γ-aminobutyric acid, but there is a possible role of short-term use in CPSP patients with anxiety. Intravenous administration of the γ-aminobutyric acid agonist thiopental, intravenous propofol, and intrathecal baclofen alleviated some pain in patients with CPSP, but oral doses of baclofen and amobarbital were ineffective. In one study, individuals who received oral tapered methylprednisolone had statistically significant less as-needed pain medication use 1 day post treatment and 1 day prior to rehabilitation discharge compared with individuals on nonsteroid management, including amitriptyline, fluvoxamine, gabapentin, pregabalin, and lamotrigine in varying combinations.
Rehabilitation
Rehabilitation begins with management of the various deficits resulting from the stroke. Barriers to treatment include cogitative and communication limitations due to the cerebrovascular event.
To date, CPSP has been difficult to treat with medical or surgical interventions. The pain in CPSP is a “false” signal being generated by the brain. Pain can be a useful symptom indicating an injury, but in CPSP there is no corporeal injury. It would be ideal if some method could be found to “connect to” and retrain the thalamus or other brain areas to the fact that there is no injury, so there should be no pain. For movement problems after stroke, mirror therapy, in which visual feedback from the reflection of the good limb helps to regularize the motor control loop, can be beneficial. This approach does not work for CPSP as typically applied (even in patients with CPSP and hemiparesis after stroke for whom mirror therapy helped the hemiparesis), nor should one expect it to because the problem is sensory pain, not a movement difficulty. Perhaps hyperesthesia in CPSP could be desensitized using mirror visual feedback by having a therapist stroke (or prick if this is less painful ) both the affected and the unaffected limb while the patient watches the reflection of the unaffected limb (which looks like the affected limb) in a parasagitally placed mirror. (Note that some movement of the limbs is helpful to increase the strength of the mirror visual feedback effect.) Controlled studies would be needed to test this approach.
Procedures
In addition to oral medications, electromyographic biofeedback, pain coping skills, and behavioral therapies including relaxation, visualization therapy, and meditation have been trialed. Transcutaneous electrical nerve stimulation with the low-frequency acupuncture like transcutaneous electrical nerve stimulation has been reported to have temporary effects.
There are some limited studies that indicate that acupuncture is helpful in CPSP. Specifically in one study visual analog pain scores decreased at 3 weeks post injection of eight individuals. Larger controlled studies are needed to assess these alternative procedures.
Surgery
When all other modalities have failed, surgical options may be considered. Motor cortex stimulation (chronic stimulation of the precentral cortex) is a procedure that has shown some improvement of CPSP, whereas sensory cortex stimulation has been noted to worsen pain.
Deep brain stimulation, insertion of stimulating electrodes into the periaquductal or periventricular gray area, specific thalamic nuclei, or the internal capsule has been trialed and in one study was effective for 70% (10/15) of the patients with CPSP, and in a case report the effects of the deep brain stimulation was still effective at the 6-month follow-up. In another patient with deep brain stimulation by an electrode implanted in his periventricular gray region, he had pain relief lasting 4 months.
Neurosurgical destructive options including sympthectomy, cordotomy, medial thalamotomy, and mesencephalic tractotomy, which in limited cases of patients with central and deafferentation pain improved the allodynia and hyperpathia, but with less promising outcome for the burning or dysesthetic pain have been trialed, but they are no longer recommended, due to the unpredictable effects and significant morbidity and mortality. Because ablation is considered the final resort, more conservative measures, including deep brain stimulation, should be tried.
Technology
No technologies have been shown useful for CPSP.
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