Pain Syndromes Associated With Cerebrovascular Accidents




Abstract


Pain after a cerebrovascular event can be extremely debilitating, affecting thousands of patients every year, as cerebrovascular events are one of the most common causes of morbidity and mortality in the United States. The four most common painful conditions in this population are central poststroke pain, shoulder hand syndrome, poststroke headache, and hemiplegic shoulder pain, with reported incidence rates ranging from 1.5% to 70%. Investigation to elucidate the pathophysiology of these conditions has concluded that central poststroke pain is a central neuropathic syndrome and shoulder hand syndrome is a form of complex regional pain syndrome; however, the etiologies of poststroke headache and hemiplegic shoulder pain are still unclear. Although some diagnostic tests may be helpful, the diagnosis for all four conditions is primarily based on the patient’s reported history as well as the physical examination. Similar to other neuropathic pain syndromes, there is no single treatment option for patients with these conditions, and multiple factors must be considered in the development of the care plan for adequate symptom management and improved function.




Keywords

Allodynia, Anticonvulsants, Antidepressants, Central poststroke pain, Cerebrovascular event, Hemiplegic shoulder pain, Modalities, Neuropathic pain, Poststroke headache, Shoulder hand syndrome, Stroke

 


Cerebrovascular events are one of the most common causes of morbidity and mortality in the United States, with nearly 800,000 new strokes yearly and a prevalence of 6.6 million in people 20 years or older. In addition to associated neurologic deficits, stroke survivors may have various pain conditions, some of which are unique to this patient population. Although there are many potential causes of chronic pain after stroke, this chapter focuses on four of the more common pain conditions that can have neuropathic etiologies: central poststroke pain (CPSP), shoulder hand syndrome, poststroke headache, and hemiplegic shoulder pain (HSP).




Central Poststroke Pain


CPSP, previously known as Dejerine-Roussy syndrome and thalamic pain syndrome, is a feared complication of cerebrovascular accidents and has been described by Tasker as “among the most spectacular, distressing, and intractable of pain syndromes.” It affects approximately 8% of patients after a stroke but is more common after strokes that involve the lateral medulla and inferior-lateral thalamus, with a prevalence of 25% and 17%–18%, respectively.


Patients primarily complain of pain within the distribution of the body affected by the stroke. The majority of patients, approximately 67%, have allodynia and may also endorse dysesthesia, hypoesthesia, or hyperpathia, whereas 40% of patients may experience hypoalgesia. The pain typically fluctuates in intensity as well as distribution throughout the day. In addition to the pain complaint, patients may present with hemiplegia as a result of the stroke, although approximately 52% do not have any weakness. They generally present with other sensory findings besides painful symptoms, such as astereognosis and altered temperature perception. Of note, the affected body area is generally objectively cooler, especially as the pain worsens. The majority of patients also have ataxia, found in up to 62%. Although a patient’s neurologic deficits as a result of the stroke are evident immediately, CPSP can present days to months after the stroke. Less than 40% of patients with CPSP are reported to develop the painful symptoms at the time of the stroke. The majority of patients have onset of symptoms within a month of the stroke, whereas 18% develop symptoms within the first 6 months and the remaining 18% develop symptoms after 6 months. Most patients have pain constantly, whereas the remaining 15% have pain daily.


In addition to the sensory and motor changes previously mentioned, on physical examination the patient has impaired pinprick, temperature, and touch sensation, as well as notable coolness of the affected area. Vibration and proprioception sensation are intact. The lowered skin temperature is attributed to autonomic instability in the area affected by the stroke. CPSP is the result of dysfunction of the spinothalamocortical tract as it courses from the spinal cord through the brainstem and thalamus to the sensory cortex.


The diagnosis of CPSP is made solely based upon the history and physical examination. Imaging can be done to rule out other diagnoses and to confirm the history of a stroke. To diagnose a patient with CPSP, the patient must have a history of a stroke or stroke-like event if no imaging has been done, pain in a neuroanatomically plausible distribution based upon the location of the stroke, and pain and temperature sensory deficits. The presence of allodynia is pathognomonic but is not required for a diagnosis of CPSP. In addition, paradoxic burning or burning pain induced with cold stimulation increases the possibility of the symptoms being attributable to CPSP but is not diagnostic.


Differential diagnosis is broad, as there are many conditions with overlapping symptoms. Depending on the location and distribution of the pain, the physician has to consider a diagnosis of multiple sclerosis, syringomyelia, peripheral neuropathy, complex regional pain syndrome (CRPS), poststroke headache, spasticity, HSP, frozen shoulder, rotator cuff tendinopathy or tear, herpes zoster, and deep venous thrombosis.


Upon evaluation of patients in whom CPSP is suspected, desensitization with various tactile stimuli is initiated, as it is commonly a first-line treatment in clinical practice. When treating these patients, there are few evidence-based nonpharmacologic and noninterventional options. A small study of 15 patients was done to examine the effects of transcutaneous electrical nerve stimulation (TENS) on CPSP. After receiving treatment, four patients had pain relief, five had a transient increase in pain, and six reported no change in their pain. In addition to this weak evidence, the painful area tends to be quite extensive to which it would be difficult, if not impossible, to adequately apply TENS pads to provide sufficient electrical stimulation. An emerging therapeutic option for CPSP is transcranial magnetic stimulation (TMS). In a prospective study of 14 patients who underwent five sessions of TMS, there was a modest improvement in pain 4 weeks after treatment with P = .018.


Pharmacologic therapeutic options include several classes of medications. The most extensively studied class is the tricyclic antidepressants, specifically amitriptyline. As amitriptyline inhibits norepinephrine and serotonin reuptake, this modulates thalamic burst firing activity, one of the proposed theories for the development of CPSP, thereby reducing pain. The side-effect profile should be considered, especially in the elderly patient with stroke, in which case adverse effects may be experienced before therapeutic benefit. Other tricyclic antidepressants such as nortriptyline, desipramine, imipramine, and doxepin have been studied less extensively. Other antidepressants that can be used are trazodone, venlafaxine, and maprotiline. Although fluvoxamine can also be tried, selective serotonin reuptake inhibitor (SSRI) antidepressants are generally ineffective.


Anticonvulsants, specifically lamotrigine, gabapentin, pregabalin, carbamazepine, and phenytoin, may be used, although supporting evidence is based primarily on case reports, therefore not placing them as first-line treatment. As with other chronic pain conditions, opioids can be trialed; however, there is no evidence demonstrating their effectiveness in CPSP and associated potential for adverse effects should be considered, especially in the elderly. Various cardiac medications have also been recommended as possible treatment options, specifically clonidine, mexiletine, and β-blockers.


More experimental pharmacologic treatments include propofol, intrathecal baclofen, ketamine, and intravenous lidocaine. A small, double-blind study consisting of six patients with CPSP receiving intravenous lidocaine showed reduction of pain for 45 min after the injection, with resumption of pain thereafter. In a double-blind randomized controlled trial studying naloxone, 3 of the 20 patients in the study had transient relief with naloxone, whereas 4 had relief with saline and an additional 4 had relief with both. If pharmacologic or therapeutic modalities are ineffective at managing the patient’s symptoms, patients may undergo a sympathetic blockade, which may provide initial pain relief that generally recurs.


Surgical options include thalamotomy or mesencephalic tractotomy in which abnormal reticulothalamic neuronal pools, a proposed source of pain, are removed. As a result, it is less likely that these pain sources are reactivated. These procedures are better at ameliorating allodynia and hyperpathia than burning pain. Dorsal root entry zone (DREZ) lesioning can also be done, but for chronic pain conditions in general, the recurrence rate 2 years after DREZ lesioning ranges from 60% to 80%. Less permanent procedures include implanted spinal cord, deep brain, and motor cortex stimulators. In a prospective study of 30 patients who underwent spinal cord stimulator trials for CPSP, 30% had good pain relief and 20% had fair pain relief, whereas the remaining 50% had poor pain relief. Ultimately, 10 of the original 30 patients underwent spinal cord stimulator placement, 9 of whom had long-term pain relief, lasting for 28 months on average. The results from studies examining the effects of deep brain stimulators on CPSP are conflicting and in limited cases have shown improvement in allodynia and improved sensory discrimination. For motor cortex stimulators, a retrospective study examined 14 patients with various diagnoses, 7 of whom had CPSP. There was evidence that the best long-term results were seen in those with CPSP as two subjects had excellent long-term results and three had satisfactory results, but the magnitude of relief waned over time.


Limited success with pharmacologic, interventional, and surgical options has resulted in having many patients explore complimentary modalities, such as acupuncture and massage. There are no studies that have examined the effects of acupuncture on CPSP, but there have been case reports of favorable results. Interestingly, there are two cases of subjects with CPSP who experienced instantaneous and sustained pain relief after vestibular caloric stimulation. Ramachandran theorizes that cold water vestibular caloric irrigation activates the posterior insula, which in turn inhibits the generation of pain in the anterior cingulate. Although this technique needs further study, if further evidence supports it, it would provide a safe pain-relief alternative for patients. Ultimately, what is most important for these patients is to learn coping and relaxation techniques as the pain is generally lifelong and can lead to depression and be aggravated by stress.


The overall course and prognosis for these patients is poor. Pain is often the most limiting symptom after their stroke. The most favorable prognostic factor is early initiation of treatment after onset of symptoms. Even if treatment is started quickly, patients may still have lifelong pain. In one survey, practitioners reported that 50% of patients experienced pain relief with medication. Like other chronic pain conditions, CPSP negatively affects the patient’s quality of life, ability to participate in rehabilitation, and quality of sleep. Given the high prevalence of stroke, the aging population, the frequency of CPSP, and the associated disability, treatments for this condition that lead to adequate analgesia are important to treat many people for years to come.




Shoulder-Hand Syndrome


CRPS is a chronic neuropathic pain condition that can develop after various musculoskeletal injuries or surgeries or as a result of injuries to the peripheral or central nervous system. In patients who had stroke, the most common form of CRPS is shoulder-hand syndrome (SHS), with an incidence ranging from 1.5% to 50%. Patients with SHS frequently report pain in the shoulder but may describe pain in the hand or both. Although the disease course can be difficult to predict, the prognosis has been found to correlate with the patient’s motor deficit, spasticity, vibratory sensory deficits, and initial coma.


To make a diagnosis of SHS, a patient must meet diagnostic criteria for CRPS of the upper limb with a history of a stroke. What complicates the diagnosis in clinical practice is that the physician must be able to tease out the findings and symptoms that are attributable to the stroke itself rather than a separate diagnosis of SHS. As stated by the Budapest Criteria, for patients to be diagnosed with CRPS, they must have pain and vasomotor, sudomotor, and motor or trophic changes. Patients with SHS may experience allodynia, hyperalgesia, hyperpathia, or thermal hyperesthesia or allodynia. There may also be vasomotor or sudomotor changes, such as temperature dysregulation, skin color change, or edema, as a result of the stroke and disuse. In regards to motor changes, it is not uncommon for patients to a have upper limb weakness after a stroke depending on the site of the lesion. In the case of SHS, the limb is weaker than expected compared with the other stroke deficits and the patient generally has a decreased range of motion and poor muscle coordination, and approximately 50% have a tremor. Just as those with CRPS, those with SHS may have trophic findings, such as nail or hair growth changes. It is also common for these patients, just like other patients with chronic pain, to have anxiety or depression as a result of the pain. The symptoms of SHS overlap with many other conditions, some of which are unique to the stroke population. A possible differential diagnosis is listed in Table 19.1 .



Table 19.1

Differential Diagnosis for Shoulder-Hand Syndrome

















Differential Diagnosis



  • Other poststroke pain conditions




    • CPSP



    • Hemiplegic shoulder pain





  • Musculoskeletal




    • Myofascial pain



    • Rotator cuff pathology



    • Tendonitis



    • Fracture



    • Subluxation



    • Osteoarthritis





  • Neurologic




    • CRPS type 1 or 2 a



    • Peripheral polyneuropathy



    • Peripheral mononeuropathy



    • Radiculopathy





  • Infectious




    • Herpes zoster



    • Cellulitis



    • Septic arthritis



    • Osteomyelitis





  • Vascular




    • Thrombus



    • Peripheral vascular disease



    • Lymphedema





  • Rheumatologic




    • Rheumatoid arthritis



    • Gout



CPSP , central poststroke pain; CRPS , complex regional pain syndrome.

a See Chapter 6 for definition.



Although the diagnosis is made clinically, there is some testing to assist in confirming the diagnosis. Traditional three-phase bone scintigraphy has been studied as a diagnostic tool for CRPS with variable sensitivity and specificity, but one study done by Park et al. showed that quantitative three-phase bone scintigraphy had a sensitivity of 80.8% and specificity of 100% for diagnosing very acute stage CRPS. In a study done by Kumar et al., dual-energy X-ray absorptiometry scan was shown to correlate with the duration and severity of SHS. There is a lack of good evidence to support the use of electromyography as a diagnostic tool to predict the development of SHS, as presence of spontaneous activity in muscles of the effected limb is correlated with the development of SHS in 65% of paretic patients, whereas only 4% of patients without spontaneous activity developed SHS. Other tests, including nuclear magnetic resonance and thermography may show abnormalities, such as bone and subcutaneous edema or reduced skin temperature, respectively, but these are not diagnostic of CRPS or SHS. Furthermore, normal findings on thermography do not rule out SHS. Stellate ganglion blocks may also be tried as a diagnostic and therapeutic tool; however, lack of improvement does not rule out SHS, as not all patients with CRPS have sympathetically mediated pain.


Rehabilitation options available for SHS help with symptom management. Although keeping the affected limb elevated can help reduce the swelling, there is no evidence to support a combination of kinesiotherapy and manual lymphatic drainage to control the edema. Desensitization is commonly used to treat CRPS and is therefore used in SHS to manage allodynia. Cacchio et al. also found that mirror therapy can lead to significant improvement in pain and motor function after 4 weeks and 6 months compared with controls. In addition to modalities that assist with cortical remapping, restricting arm movement has also been shown to be helpful. Kondo et al. found a significant reduction in the development of SHS when passive movement of the upper limb affected by the stroke was restricted. Also, Hartwig et al. showed that a shoulder joint functional orthosis reduced SHS symptoms compared with the control group.


In addition to therapeutic modalities, multiple classes of medications can be used to manage the painful symptoms. Nonsteroidal antiinflammatory medications may be of most use in the early phase of SHS; however, the efficacy is low. Tricyclic antidepressants are also used, as they can reduce neuropathic pain and improve mood and sleep. These medications must be used with caution in the elderly population given the anticholinergic side-effect profiles. Unfortunately, other classes of antidepressants, specifically SSRIs, have not been found to be efficacious in treating neuropathic pain. Antiepileptics, specifically gabapentin, have been used to treat various sources of neuropathic pain and may be useful in the treatment of SHS; however, this has not been studied. Although topical medications have moderate efficacy in treating CRPS, they are not often used for SHS. Capsaicin, lidocaine, and dimethylsulfoxide cream may be used, especially if oral medications prove ineffective or cannot be tolerated. Opioids are the last pharmacologic option in the treatment of SHS, as they have not been studied as a treatment for CRPS, let alone SHS, and are associated with other side effects and concerns. There are currently preliminary studies examining the effects of botulinum toxin and thalidomide, as well as a case reporting the benefit of bisphosphonates in the treatment of SHS. These treatment options require further study.


If pain persists despite these treatments, a sympathetic or somatic block can be performed. A sympathetic block is generally attempted first, but it generally reduces pain only if the pain is sympathetically mediated. As previously stated, not all patients with CRPS have sympathetically mediated pain; therefore such a block may not be effective. If a sympathetic block is successful, the patient should immediately start physical and occupational therapy. If there is no relief after a sympathetic block, a somatic block can be performed. This can be done either at the brachial plexus or as an epidural. Unfortunately, the literature in support of these interventions is scarce and primarily anecdotal. Spinal cord stimulators and intrathecal analgesia with opioids, ziconitide, or clonidine have also been used in the treatment of CRPS and SHS and may be an option for patients who have uncontrollable pain.


There are few surgical options for patients with intractable SHS. Sympathectomies can be performed surgically, chemically, or via radiofrequency ablation. Although these may provide pain relief initially, it is rarely permanent and patients may develop new pain syndromes that prove to be just as difficult to control. As a result, this procedure is generally avoided. A Cochrane review of sympathectomies in the treatment of SHS showed sympathectomies are not effective for neuropathic pain relief overall and can lead to significant complications. If all else fails and if a patient is properly counseled, some patients choose to have the affected limb amputated. Patients must understand that only a small percentage experience pain relief and that new pain syndromes and problems may arise as a result of the amputation.


Just as in CPSP, what is critical for these patients is proper psychological support, including counseling and relaxation, and biofeedback techniques to manage the chronic pain as well as depression that can develop as a result of chronic pain and stroke.




Poststroke Headache


Both headaches and strokes are individually quite prevalent, and headaches that occur at the onset of stroke have been well studied and occur in 27%–31%. What is less clear is the prevalence and disease course of poststroke headache. This is described as a headache that is associated with the stroke and persists after completion of the stroke. This type of headache has a reported incidence ranging from 10.8% to 23.3%, although most studies report a range between 10% and 12%. The headaches are primarily tension type but may present as migraine type or a combination of both. Patients with poststroke headache most often describe the pain as a pressing sensation and generally deny change in headache with movement or associated photophobia, phonophobia, nausea, or vomiting. Those with poststroke headache may have daily headaches or headaches a few times a month, and the headaches can range in duration from less than an hour to constant pain. The pain can also range in severity but is generally reported as moderate to severe. Although there are no distinct diagnostic criteria for poststroke headache, the onset of the headache at onset of stroke is the most important distinguishing factor between stroke-attributed and non-stroke-attributed headaches.


Patients are more likely to develop poststroke headache if the stroke is in the right hemisphere, specifically in the temporal lobe. A history of headaches before stroke also increases the risk of developing poststroke headache with a rate of 17.3% compared with 4.1% in patients without a history of headaches. Interestingly, there is no increased risk of developing headache after a hemorrhagic versus ischemic stroke. At this time, the overall course and prognosis is not well described; however, a headache at stroke onset is predictive of poststroke headache 6 months after the stroke.


When assessing a patient who had a stroke and is complaining of headache, the differential diagnosis is quite broad, some of which are included in Table 19.2 . Interestingly, medication overuse headache was found to be the cause of headache in 11.5% of patients with stroke in a study done by Hansen et al.


Jun 17, 2019 | Posted by in NEUROLOGY | Comments Off on Pain Syndromes Associated With Cerebrovascular Accidents

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