Central poststroke pain in young ischemic stroke survivors in the Helsinki Young Stroke Registry Hanna Harno, MD, PhD Elena Haapaniemi, MD, PhD Jukka Putaala, MD, PhD Maija Haanpää, MD, PhD Jyrki P. Mäkelä, MD, PhD Eija Kalso, MD, PhD Turgut Tatlisumak, MD, PhD
Correspondence to Dr. Harno: [email protected]
ABSTRACT
Objective: We describe the frequency, duration, clinical characteristics, and radiologic correlates of central poststroke pain (CPSP) in young ischemic stroke survivors in a prospective study setting.
Methods: A questionnaire of pain and sensory abnormalities and EQ-5D quality-of-life questionnaire were sent to all 824 surviving and eligible patients of the Helsinki Young Stroke Registry. Patients (n 5 58) with suspected CPSP were invited to a clinical visit and filled in the PainDETECT, Brief Pain Inventory, and Beck Depression Inventory questionnaires. Results: Of the included 824 patients, 49 had CPSP (5.9%), 246 patients (29.9%) had sensory abnormality without CPSP, and 529 patients (64.2%) had neither sensory abnormality nor CPSP. The median follow-up time from stroke was 8.5 years (interquartile range 5.0–12.1). Patients with CPSP had low quality of life compared to those with sensory abnormality without CPSP (p 5 0.007) as well as to those with no sensory abnormality and no CPSP (p , 0.001). Forty (82%) of the patients with CPSP had concomitant other pain. CPSP was associated with moderate (p , 0.001) and severe (p , 0.001) stroke symptoms, but there was no difference in age at stroke onset or subtype of stroke according to the TOAST classification between the groups. Stroke localization was not correlated with CPSP. Conclusions: Late persistent CPSP was found in 5.9% of young stroke survivors and was associated with concomitant other pain, impaired quality of life, and moderate or severe stroke symptoms. Neurology® 2014;83:1147–1154 GLOSSARY ADL 5 activities of daily living; BPI 5 Brief Pain Inventory; CPSP 5 central poststroke pain; MCA 5 middle cerebral artery; NIHSS 5 NIH Stroke Scale; PCA 5 posterior cerebral artery; TOAST 5 Trial of Org 10172 in Acute Stroke Treatment.
Stroke-induced chronic pain includes a heterogeneous group of conditions such as hemiplegic shoulder pain, pain due to spasticity, headache, joint pain, and central poststroke pain (CPSP).1 In addition, stroke survivors may have other pains unrelated to stroke. CPSP is defined as “pain arising as a direct consequence of a cerebrovascular lesion of the somatosensory system in the central nervous system.”2 Recently, a grading system for CPSP diagnostics has been introduced.3 There, CPSP is defined as possible, probable, or definite according to clinical and brain imaging findings with an ischemic or hemorrhagic lesion. According to population-based studies, the prevalence of CPSP is 1% to 8% in unselected stroke patients.1,4,5 Patients with CPSP may be younger than the general stroke population.6 Young stroke patients’ outcome has challenges because of poor functional outcome and psychosocial problems.7 The aim of the present study was to describe the frequency, onset, clinical characteristics, and radiologic correlates of CPSP in detail in a large cohort of young ischemic stroke survivors8,9 using the grading system for CPSP.3 METHODS The study was conducted at the Department of Neurology, Helsinki University Central Hospital. It serves a population of 1.5 million as the only neurologic emergency unit. The study population consisted of 1,008 consecutive patients from the Helsinki Young Stroke Registry8 with first-ever ischemic stroke when aged 15 to 49 years. Patients were treated at the Department of Neurology, Helsinki University Central Hospital between 1994 and 2007. From the Departments of Neurology (H.H., E.H., J.P., T.T.), Neurosurgery (M.H.), and Anesthesiology (E.K.), and BioMag Laboratory, HUS Medical Imaging Center (J.P.M.), Helsinki University Central Hospital; and Etera Mutual Pension Insurance Company (M.H.), Helsinki, Finland. Go to Neurology.org for full disclosures. Funding information and disclosures deemed relevant by the authors, if any, are provided at the end of the article. © 2014 American Academy of Neurology
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All surviving patients in the registry in 2010 received a questionnaire (n 5 824)9 (figure 1), and those who did not respond within 2 months were sent a reminder. The questionnaire included questions on the presence of chronic pain (pain duration for at least 3 months) and its intensity, interference, suspected cause(s) and current treatment, body templates for marking the location of pain and location of abnormal sensory symptoms, and the EQ-5D quality-of-life questionnaire.10 Patients with insufficient communication or cognitive performance and those with a severe psychiatric disorder were excluded. Patients with suspected CPSP were interviewed via telephone using a structured questionnaire. If the telephone interview supported a possible diagnosis of CPSP, the patient was invited to a clinical visit including medical history and clinical examination (general and neurologic examination). Sensory examination included testing of tactile sensation with a piece of cotton wool, pinprick sensation with a sharp wooden cocktail-stick, cold and warm sensation with a cold and a warm water tube, respectively, presence of dynamic mechanical allodynia with a camel-hair brush, and presence of static mechanical allodynia with compression of the skin with a finger.11 At the visit, functional status of patients in their activities of daily living (ADL) was assessed using the scale completely independent/light assistance needed/full assistance needed. Mobilization was assessed with the scale normal/cane or crutches needed/ wheelchair needed and patients’ current working status with a scale working full time/working part time/retired. In addition to CPSP, other pains were diagnosed. Patients having other pain(s) in addition to CPSP were asked to rate which pain was the worst one. The onset of CPSP was queried and coded as follows: during the first week after stroke, between the first week and the first month after stroke, after 1 month but before 6 months after stroke, after 6 months but before 12 months from stroke, and after 12 months from stroke. The treatment of CPSP was coded. The patients with CPSP were asked about their previous medication with shown efficacy for neuropathic pain.12 The patients also named their worst health problem. At the visit, patients filled in 3 questionnaires: PainDETECT,13 Brief Pain Inventory (BPI),14 and Beck Depression Inventory IA.15 PainDETECT is a neuropathic pain screening tool that incorporates a self-report questionnaire with 9 items. There are 7 sensory descriptors (burning pain, tingling or prickling pain, light touch being painful, electric shock-like pain, cold or heat being painful, numbness, slight pressure being painful) with 6 response options (from “never” to “very strong”). Two items relate to the spatial (radiating) and temporal characteristics of the individual pain pattern. Cutoff scores #12 (a neuropathic component is unlikely) and $19 (a neuropathic component is likely) were used.13 The BPI is a numeric rating scale questionnaire with questions about the severity of pain (Severity Scale) and its impact on daily living (Interference Scale).14 Included patients were divided into 3 distinct clinical groups: those with CPSP, those with sensory abnormality but not CPSP, and those with no sensory abnormality. These groups were compared for sex, age at onset of stroke and at follow-up, stroke location, lesion size, and subtype of stroke (Trial of Org 10172 in Acute Stroke Treatment [TOAST]),16 history of recurrent ischemic stroke, and quality of life at follow-up. Location of stroke was defined as anterior, posterior, or both territories. We categorized lesion size as follows: (1) small, i.e., ,1.5 cm lesion in anterior or posterior circulation; (2) medium, i.e., lesion in a cortical superficial branch of the anterior cerebral artery, middle cerebral artery (MCA), or 1148
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posterior cerebral artery (PCA), or deep branch of MCA or PCA, or in internal border-zone territories; (3) large anterior, i.e., lesion involving complete territory of anterior cerebral artery or MCA, 2 branches of MCA, or .1 artery territory; and (4) large posterior, i.e., lesion .1.5 cm, involving brainstem, cerebellum, or entire territory of PCA including border-zone territories.17
Standard protocol approvals, registrations, and patient consents. The local ethics committee approved the study, and all participating patients gave their written informed consent.
Statistical analyses. The data are presented as means with SDs, medians with interquartile ranges, or counts with percentages. Pairwise comparisons between the 3 clinical subgroups were performed using x2, Fisher exact, and Mann–Whitney U tests, when appropriate. Logistic regression analysis with backward stepwise algorithm was constructed to study baseline factors associated with the occurrence of CPSP. Here, patients with CPSP were separately compared with (1) those with sensory abnormality but not CPSP, and (2) those with no sensory abnormality. Age and sex were forced in the models and variables significant in the univariate comparisons were then entered in the models. All analyses used SPSS 20 for Macintosh (IBM Inc., Armonk, NY). A 2tailed p value .0.05 was considered significant.
The median follow-up time from the stroke was 8.5 years (interquartile range 5.0–12.1), with longer follow-up time for patients without CPSP (9.3 years for those with sensory abnormality and 8.3 years for those without). Of the included 824 patients, 49 patients (5.9%) had CPSP, 246 (29.9%) had sensory abnormality without CPSP, and 529 (64.2%) had no sensory abnormality (figure 1). There was no difference in age at stroke onset or at follow-up, or subtype of stroke according to the TOAST classification between the groups. Compared with both comparator groups, strokes were more severe when measured with the NIHSS score among patients with CPSP. Regarding stroke territory, laterality, or anatomical distribution, no differences were found between the groups. However, lesions were larger and hemorrhagic transformation of the infarction occurred more often in patients with CPSP compared with those without CPSP or those with any sensory abnormality. After adjustment for NIHSS score, no significant correlation between hemorrhagic transformation and CPSP remained (odds ratio 1.78, 95% confidence interval 0.74–4.28; p 5 0.195). Quality of life was worse in patients with CPSP compared with both comparator groups (table). In the logistic regression analysis (adjusted for age, sex, and hemorrhagic transformation) comparing patients with CPSP to patients without any sensory abnormality, moderate (odds ratio 4.94, 95% confidence interval 2.3–10.45; p , 0.001) and severe (5.36, 2.21–12.96; p , 0.001) symptoms were associated with the occurrence of CPSP. In a similar analysis in which patients with CPSP were compared to those with sensory abnormality without CPSP (adjusted for age and sex), severe symptoms
RESULTS
Figure 1
Study population flowchart
CPSP 5 central poststroke pain.
(measured using the NIHSS) were associated more with CPSP (2.51, 1.01–6.23; p 5 0.047). Of the patients with CPSP, 31 (63%) were independent in their ADL, 17 (35%) needed partial
assistance, and 1 (2%) needed full assistance. Mobility was normal in 25 (51%), whereas 21 (43%) needed a cane or crutches, and 3 (6%) needed a wheelchair. Twelve (24%) of them were working full Neurology 83
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Table
Univariate comparison of patients with (1) neither sensory abnormality nor CPSP, (2) with sensory abnormality but without CPSP, and (3) with CPSP
All (N 5 824)
No sensory abnormality, no CPSP (n 5 529)
CPSP (n 5 49)
p for CPSP vs no sensory abnormality, no CPSP
Female sex
325 (39.4)
205 (38.8)
98 (39.8)
22 (44.9)
0.399
Age at stroke onset, y
40.7 (7.8)
40.2 (8.2)
41.5 (7.1)
41.3 (7.3)
0.503
NIHSS score
Sensory abnormality, no CPSP (n 5 246)
3 (1–5)
2 (1–4)
3 (2–8)
4 (3–12)
0–6 (mild)
677 (82.2)
466 (88.1)
182 (74.0)
29 (59.2)
7–14 (moderate)
95 (11.5)
39 (7.4)
44 (17.9)
12 (24.5)
‡15 (severe)
52 (6.3)
24 (4.5)
20 (8.1)
8 (16.3)
Lesion size Small
377 (45.8)
248 (46.9)
110 (44.7)
Moderate
240 (29.1)
171 (32.3)
60 (24.4)
9 (18.4)
Large posterior
97 (11.8)
64 (12.1)
28 (11.4)
5 (10.2)
Large anterior
110 (13.3)
46 (8.7)
48 (19.5)
16 (32.7)
Anterior
413 (50.1)
255 (48.2)
131 (53.3)
27 (55.1)
Posterior
379 (46.0)
255 (48.2)
103 (41.9)
21 (42.9)
Both
32 (3.9)
19 (3.6)
12 (4.9)
1 (2.0)
Lateralityb 355 (44.8)
222 (43.4)
111 (46.8)
0.510 0.658 a
,0.001
0.004a
,0.001a
0.234
0.601
0.676
0.186
0.343
19 (38.8)
Territory
Right
p for CPSP vs sensory abnormality, no CPSP
22 (48.9)
Left
362 (45.6)
234 (45.8)
106 (44.7)
22 (48.9)
Both
76 (9.6)
55 (10.8)
20 (8.4)
1 (2.2)
333 (40.4)
202 (38.2)
108 (43.9)
23 (46.9)
0.229
0.696
Anatomical location Cortical Subcortical
386 (46.8)
239 (45.2)
118 (48.0)
29 (59.2)
0.060
0.152
Thalamus
92 (11.2)
63 (11.9)
24 (9.8)
5 (10.2)
0.723
1.000
Basal ganglia
187 (22.7)
117 (22.1)
60 (24.4)
10 (20.4)
0.782
0.550
Cerebellum or brainstem
262 (31.8)
172 (32.5)
78 (31.7)
12 (24.5)
0.249
0.316
81 (9.8)
38 (7.2)
35 (14.2)
8 (16.3)
0.046a
0.704
0.866
0.939
Hemorrhagic transformation TOAST subgroup LAA
47 (5.7)
26 (4.9)
17 (6.9)
4 (8.2)
CE
160 (19.4)
105 (19.8)
44 (17.9)
11 (22.4)
SVO
111 (13.5)
69 (13.0)
36 (14.6)
6 (12.2)
OTH
219 (26.6)
142 (26.8)
65 (26.4)
12 (24.5)
UND
287 (34.8)
187 (35.3)
84 (34.1)
16 (32.7)
49.2 (9.1)
48.5 (9.3)
50.6 (8.4)
49.3 (8.8)
Age at follow-up, y EuroQoL VAS
80 (68–88)
80 (70–90)
75 (60–80)
70 (50–80)
0.749
0.360 a
,0.001
0.007a
Abbreviations: CE 5 cardioembolism; CPSP 5 central poststroke pain; LAA 5 large-artery atherosclerosis; NIHSS 5 NIH Stroke Scale; OTH 5 other determined etiology; SVO 5 small-vessel occlusion; TOAST 5 Trial of Org in Acute Stroke Treatment; UND 5 undetermined etiology; VAS 5 visual analog scale. Data are mean (SD), median (interquartile range), or n (%). a Significant values. b Thirty-one brainstem lesions were unclassifiable.
time, 2 (4%) were working part time, and 35 (71%) were retired. The onset of CPSP was between the first week and the first month after stroke in most cases (figure 2). 1150
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In patients with CPSP, the mean (SD) pain intensity in BPI was 5.3 (2.0) and the pain interference was 4.5 (2.7). Ten (20%) of the patients with CPSP rated their pain as mild, 26 (53%) moderate, 11 (22%) severe,
Figure 2
Onset of CPSP from stroke
Temporal distribution of the onset point of central poststroke pain (CPSP) from stroke.
and 2 (4%) as excruciating. Pain interference was graded as minimal by 3 patients (6%), mild by 14 patients (29%), moderate by 21 patients (43%), severe by 7 patients (14%), and very severe by 3 patients (6%). The mean (SD) Beck depression score in patients with CPSP was 11.5 (9.2), suggesting mild depression. Of the 49 patients with CPSP, 30 (61%) rated pain as their worst health problem. Nine patients (18%) named other neurologic symptoms (motor paresis, fatigue, visual disturbances), 3 patients (6%) depression or anxiety, and 7 patients (14%) any other symptom as their worst health problem. In addition to CPSP, 40 patients (82%) experienced other pain: musculoskeletal pain unrelated to stroke (10 patients), primary headache (5 patients), painful polyneuropathy (3 patients), and other stroke-associated non-CPSP pain (22 patients). Of the 22 patients, 8 had spasticity-related pain, 9 had joint pain, 4 had both spasticity-related and joint pain, and 1 had postcraniectomy headache. Of those who had CPSP and concomitant other pain, 26 (65%) regarded CPSP as their worst pain. In addition, another 130 of the 824 stroke patients (16%) reported non-CPSP pain, i.e., joint pain, back pain, headache, polyneuropathy. Twenty-eight (57%) of the patients with CPSP used regular pain medication: simple analgesics (24 patients), mild opioids (10 patients), gabapentinoids (8 patients), amitriptyline (2 patients), and lamotrigine (1 patient). None of the patients were on strong opioids. A total of 31 patients with moderate or severe CPSP did not use neuropathic pain medication. Eight of them had tried neuropathic pain medications, but abandoned the medication because of adverse effects and/or unsatisfactory pain relief.
PainDETECT questionnaire was adequately completed by 48 patients with CPSP. The current pain intensity was 5 (mean) (SD 2.2), the worst pain and the mean pain during the previous 30 days were 8 (1.9) and 5.5 (1.8), respectively. Pain was in most cases continuous with several worsening attacks in between (46%). Only 15% of the patients (7 of 48) reported radiating pain. The mean (SD) PainDETECT score was 17 (5.7) and it was $19 in 35% of the patients (17 of 48 patients). The pain and sensory symptoms that scored higher than 3 (strong or very strong) were tingling pain (26 of 48 patients, 54%), electric shocks (14 of 48, 29%), and warm or cold allodynia (14 of 48, 29%). Numbness was scored strong or very strong by 46% of patients (22 of 48). In the sensory examination, hypoesthesia to warm was found in 29 patients (62%), to cold in 20 (43%), to pinprick in 13 (28%), and to touch in 11 patients (23%). Hyperesthesia to pinprick was found in 17 (36%), to cold in 6 (13%), and to warm in 6 (13%). Dysesthesia was present to touch in 30 patients (62%), to cold in 5 (11%), and to warm in 4 patients (9%). Dynamic mechanical allodynia was found in 10 (21%) and static mechanical allodynia in 7 patients (15%). Of the sensory abnormalities, hypoesthesia was found in 10 (21%), hyperesthesia or allodynia in 11 (23%), and a combination of them as the most frequent finding in 26 patients (55%). Any kind of allodynia was found in 21 patients (45%) with CPSP: cold allodynia was the most frequent in 14 patients (29%), warm allodynia in 5 (10%), and mechanical allodynia in 2 patients (4%). In this large, well-defined cohort of consecutive young ischemic stroke survivors, the occurrence of CPSP was 5.9%. Severe strokes with hemorrhagic transformation were more likely to associate with CPSP. The anatomical localization of stroke was diverse to cause CPSP. Moreover, patients with CPSP had worse quality of life than patients in comparator groups. Most of the patients had survived well from stroke with most of them independent in their ADL and mobility, but the majority were on retirement. Most patients with CPSP reported moderate pain, mild depression, and reduced quality of life. Our CPSP rate of 5.9% is in accordance with 2 Danish population-based studies of older age groups.1,4 According to the replies to the postal questionnaire, 30% of the stroke survivors had a subjective sensory abnormality without CPSP in our study (figure 1). Based on the CPSP classification,3,18 42 of our patients had definite and 7 had probable CPSP. Four patients with probable CPSP had no findings in neuroimaging and 2 had not been clinically examined, but had an ischemic lesion in brain CT or DISCUSSION
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Figure 3
Pain drawings of patients with central poststroke pain (CPSP)
The patients drew pain areas; those marked in gray are located in the back of the body.
MRI,8 both valid for detecting ischemic and hemorrhagic lesions. In sensory examination, all but one of the examined patients had abnormal findings compatible with a lesion of the somatosensory system and with their body pain areas (figure 3). Central pain, including CPSP, may arise from an imbalance of facilitatory and inhibitory systems that include interactions among the spinal cord, the nuclei of the brainstem, and supraspinal thalamocortical circuits.2 Thus, various kinds of stroke lesions may cause 1152
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CPSP. However, in some studies, lateral medullary infarction or lesions in the ventroposterior part of the thalamus were related to a high prevalence of CPSP (25% and 18%, respectively).19,20 In our study, there was no correlation regarding stroke localization. However, stroke severity with hemorrhagic transformation correlated with the presence of CPSP. A previous study has also reported a correlation between hemorrhagic transformation and CPSP. In that study, many of the lesions were thalamic, which was considered the most likely cause of CPSP.21 Our study suggests a risk of developing CPSP if a young stroke patient has a large ischemic lesion with hemorrhagic transformation. Nevertheless, with our sample size, hemorrhagic transformation did not remain as an independently associated risk factor for developing CPSP. A large study on chronic pain syndromes after ischemic stroke (Prevention Regimen for Effectively avoiding Second Stroke [PRoFESS] Trial) reported that 431 of 15,754 patients had CPSP (2.7%), a prevalence lower than ours.22 Younger age and stroke severity were significant predictors for CPSP, in line with our findings. Some type of allodynia occurred in 45% of our patients with CPSP. An even higher prevalence of allodynia (71%) has been reported.6 Cold allodynia, pinprick hyperalgesia, and dysesthesia in response to touch were common findings in our study and in line with a previous finding.1 Cold allodynia was by far the most common type of allodynia in our series. In accordance with previous reports, CPSP appeared during the first month after stroke in most cases,4 was at least of moderate intensity in most patients, and interfered at least moderately with daily life in most patients.1 Our patients with CPSP had lower quality of life than stroke survivors without CPSP, in line with a previous report.23 PainDETECT has previously been used for identifying different sensory profiles of peripheral neuropathic pain, such as postherpetic neuralgia and painful diabetic neuropathy.24 It has not previously been used to define CPSP. Tingling or electric shocklike pain, cold or warm allodynia, and numbness were the most common descriptors of pain in PainDETECT in our patients with CPSP. This is in line with the 7-item Douleur Neuropathique 4 questionnaire25 that was used in a previous CPSP study.26 However, it remains uncertain whether PainDETECT as such is useful as a screening tool for CPSP. In our study, the mean points in PainDETECT were moderate (17). The sum of scores $19 indicates that neuropathic pain is likely. Originally, the PainDETECT validation was performed for patients with chronic low back pain. In PainDETECT, the patient receives 2 additional scores if there is radiating pain. This is logical for neuropathic
type of low back pain, but, according to our study, not useful for CPSP. A modified PainDETECT could be developed for central neuropathic pain with additional scores if the patient reports tingling or electric shocktype pain, or warm or cold allodynia. Patients with CPSP frequently experience concomitant musculoskeletal pain,1,2,27 which was the case in most of our patients with CPSP as well. Most of our patients receiving pain treatment used simple analgesics, whereas the use of neuropathic pain medication was less common. This may reflect underuse of appropriate analgesics, insufficient response to neuropathic pain treatment, intolerable side effects, or underuse of medication. Only 26% of our patients with CPSP with moderate or severe pain had ever been offered neuropathic pain medications, which may reflect the underdiagnostics of CPSP. More emphasis should be applied to effective management of pain immediately after the diagnosis. However, CPSP can be rather resistant to pharmacologic management with drugs that are recommended for pain treatment of CPSP. Therefore, new approaches for difficult-to-treat central pain, e.g., transcranial magnetic stimulation, are needed.28–30 This study has some limitations. The clinical examination did not include quantitative sensory testing. However, to perform quantitative sensory testing in all of the patients with sensory abnormality (295 patients) would have been costly, not particularly feasible, and not required for definite CPSP diagnosis according to CPSP classification. Not all of our CPSP candidates attended clinical examination and 4 of them had no initial findings in neuroimaging. Brain MRI was not done in all patients and thus the lesion characterization relied on CT in some patients. Thus, volumetric studies of the stroke lesions could not be done. Strengths of our study are the large, virtually population-based cohort, meticulous clinical examination of the patients, and the use of the grading system for CPSP diagnosis. In a young stroke patient population, 1 of 17 developed CPSP. CPSP was more likely in stroke patients with a severe stroke regardless of sex and age and was often associated with other types of pain. Quality of life worsens with CPSP and pain may thus negatively affect acute and chronic stroke rehabilitation. AUTHOR CONTRIBUTIONS H.H. analyzed and interpreted the data, drafted the manuscript, and contributed to the scientific content. E.H. designed the study, collected data, examined patients, contributed to the scientific content, and revised the manuscript. J.P. designed the study, performed advanced statistical analyses of the data, interpreted the data, drafted the manuscript, and contributed to the scientific content. M.H. designed the study, drafted the manuscript, collected data, examined the patients, and contributed to the scientific content. J.P.M. contributed to the scientific content and revised the manuscript. E.K. contributed to the scientific content and revised the manuscript. T.T. designed and supervised the study, revised the manuscript, and contributed to the scientific content.
STUDY FUNDING Supported by the Helsinki University Central Hospital Research Funds.
DISCLOSURE The authors report no disclosures relevant to the manuscript. Go to Neurology.org for full disclosures.
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Bouhassira D, Attal N, Alchaar H, Boureau F, Brochet B, Bruxelle J. Comparison of pain syndromes associated with nervous or somatic lesions and development of a new neuropathic pain diagnostic questionnaire (DN4). Pain 2005; 114:29–36. Hansen AP, Marcussen NS, Klit H, Andersen G, Finnerup NB, Jensen TS. Pain following stroke: a prospective study. Eur J Pain 2012;16:1128–1136. de Oliveira RA, de Andrade DC, Machado AG, Teixeira MJ. Central poststroke pain: somatosensory abnormalities and the presence of associated myofascial pain syndrome. BMC Neurol 2012;12:89. Finnerup NB, Sindrup SH, Jensen TS. The evidence for pharmacological treatment of neuropathic pain. Pain 2010;150:573–581. Leung A, Donohue M, Xu R, et al. rTMS for suppressing neuropathic pain: a meta-analysis. J Pain 2009;10:1205– 1216. Dworkin RH, O’Connor AB, Kent J, et al. Interventional management of neuropathic pain: NeuPSIG recommendations. Pain 2013;154:2249–2261.
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Central poststroke pain in young ischemic stroke survivors in the Helsinki Young Stroke Registry Hanna Harno, Elena Haapaniemi, Jukka Putaala, et al. Neurology 2014;83;1147-1154 Published Online before print August 15, 2014 DOI 10.1212/WNL.0000000000000818 This information is current as of August 15, 2014 Updated Information & Services
including high resolution figures, can be found at: http://www.neurology.org/content/83/13/1147.full.html
References
This article cites 28 articles, 9 of which you can access for free at: http://www.neurology.org/content/83/13/1147.full.html##ref-list-1
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This article, along with others on similar topics, appears in the following collection(s): Central pain http://www.neurology.org//cgi/collection/central_pain Neuropathic pain http://www.neurology.org//cgi/collection/neuropathic_pain Stroke in young adults http://www.neurology.org//cgi/collection/stroke_in_young_adults
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Neurology ® is the official journal of the American Academy of Neurology. Published continuously since 1951, it is now a weekly with 48 issues per year. Copyright © 2014 American Academy of Neurology. All rights reserved. Print ISSN: 0028-3878. Online ISSN: 1526-632X.
Correspondence to Dr. Harno: [email protected]
ABSTRACT
Objective: We describe the frequency, duration, clinical characteristics, and radiologic correlates of central poststroke pain (CPSP) in young ischemic stroke survivors in a prospective study setting.
Methods: A questionnaire of pain and sensory abnormalities and EQ-5D quality-of-life questionnaire were sent to all 824 surviving and eligible patients of the Helsinki Young Stroke Registry. Patients (n 5 58) with suspected CPSP were invited to a clinical visit and filled in the PainDETECT, Brief Pain Inventory, and Beck Depression Inventory questionnaires. Results: Of the included 824 patients, 49 had CPSP (5.9%), 246 patients (29.9%) had sensory abnormality without CPSP, and 529 patients (64.2%) had neither sensory abnormality nor CPSP. The median follow-up time from stroke was 8.5 years (interquartile range 5.0–12.1). Patients with CPSP had low quality of life compared to those with sensory abnormality without CPSP (p 5 0.007) as well as to those with no sensory abnormality and no CPSP (p , 0.001). Forty (82%) of the patients with CPSP had concomitant other pain. CPSP was associated with moderate (p , 0.001) and severe (p , 0.001) stroke symptoms, but there was no difference in age at stroke onset or subtype of stroke according to the TOAST classification between the groups. Stroke localization was not correlated with CPSP. Conclusions: Late persistent CPSP was found in 5.9% of young stroke survivors and was associated with concomitant other pain, impaired quality of life, and moderate or severe stroke symptoms. Neurology® 2014;83:1147–1154 GLOSSARY ADL 5 activities of daily living; BPI 5 Brief Pain Inventory; CPSP 5 central poststroke pain; MCA 5 middle cerebral artery; NIHSS 5 NIH Stroke Scale; PCA 5 posterior cerebral artery; TOAST 5 Trial of Org 10172 in Acute Stroke Treatment.
Stroke-induced chronic pain includes a heterogeneous group of conditions such as hemiplegic shoulder pain, pain due to spasticity, headache, joint pain, and central poststroke pain (CPSP).1 In addition, stroke survivors may have other pains unrelated to stroke. CPSP is defined as “pain arising as a direct consequence of a cerebrovascular lesion of the somatosensory system in the central nervous system.”2 Recently, a grading system for CPSP diagnostics has been introduced.3 There, CPSP is defined as possible, probable, or definite according to clinical and brain imaging findings with an ischemic or hemorrhagic lesion. According to population-based studies, the prevalence of CPSP is 1% to 8% in unselected stroke patients.1,4,5 Patients with CPSP may be younger than the general stroke population.6 Young stroke patients’ outcome has challenges because of poor functional outcome and psychosocial problems.7 The aim of the present study was to describe the frequency, onset, clinical characteristics, and radiologic correlates of CPSP in detail in a large cohort of young ischemic stroke survivors8,9 using the grading system for CPSP.3 METHODS The study was conducted at the Department of Neurology, Helsinki University Central Hospital. It serves a population of 1.5 million as the only neurologic emergency unit. The study population consisted of 1,008 consecutive patients from the Helsinki Young Stroke Registry8 with first-ever ischemic stroke when aged 15 to 49 years. Patients were treated at the Department of Neurology, Helsinki University Central Hospital between 1994 and 2007. From the Departments of Neurology (H.H., E.H., J.P., T.T.), Neurosurgery (M.H.), and Anesthesiology (E.K.), and BioMag Laboratory, HUS Medical Imaging Center (J.P.M.), Helsinki University Central Hospital; and Etera Mutual Pension Insurance Company (M.H.), Helsinki, Finland. Go to Neurology.org for full disclosures. Funding information and disclosures deemed relevant by the authors, if any, are provided at the end of the article. © 2014 American Academy of Neurology
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All surviving patients in the registry in 2010 received a questionnaire (n 5 824)9 (figure 1), and those who did not respond within 2 months were sent a reminder. The questionnaire included questions on the presence of chronic pain (pain duration for at least 3 months) and its intensity, interference, suspected cause(s) and current treatment, body templates for marking the location of pain and location of abnormal sensory symptoms, and the EQ-5D quality-of-life questionnaire.10 Patients with insufficient communication or cognitive performance and those with a severe psychiatric disorder were excluded. Patients with suspected CPSP were interviewed via telephone using a structured questionnaire. If the telephone interview supported a possible diagnosis of CPSP, the patient was invited to a clinical visit including medical history and clinical examination (general and neurologic examination). Sensory examination included testing of tactile sensation with a piece of cotton wool, pinprick sensation with a sharp wooden cocktail-stick, cold and warm sensation with a cold and a warm water tube, respectively, presence of dynamic mechanical allodynia with a camel-hair brush, and presence of static mechanical allodynia with compression of the skin with a finger.11 At the visit, functional status of patients in their activities of daily living (ADL) was assessed using the scale completely independent/light assistance needed/full assistance needed. Mobilization was assessed with the scale normal/cane or crutches needed/ wheelchair needed and patients’ current working status with a scale working full time/working part time/retired. In addition to CPSP, other pains were diagnosed. Patients having other pain(s) in addition to CPSP were asked to rate which pain was the worst one. The onset of CPSP was queried and coded as follows: during the first week after stroke, between the first week and the first month after stroke, after 1 month but before 6 months after stroke, after 6 months but before 12 months from stroke, and after 12 months from stroke. The treatment of CPSP was coded. The patients with CPSP were asked about their previous medication with shown efficacy for neuropathic pain.12 The patients also named their worst health problem. At the visit, patients filled in 3 questionnaires: PainDETECT,13 Brief Pain Inventory (BPI),14 and Beck Depression Inventory IA.15 PainDETECT is a neuropathic pain screening tool that incorporates a self-report questionnaire with 9 items. There are 7 sensory descriptors (burning pain, tingling or prickling pain, light touch being painful, electric shock-like pain, cold or heat being painful, numbness, slight pressure being painful) with 6 response options (from “never” to “very strong”). Two items relate to the spatial (radiating) and temporal characteristics of the individual pain pattern. Cutoff scores #12 (a neuropathic component is unlikely) and $19 (a neuropathic component is likely) were used.13 The BPI is a numeric rating scale questionnaire with questions about the severity of pain (Severity Scale) and its impact on daily living (Interference Scale).14 Included patients were divided into 3 distinct clinical groups: those with CPSP, those with sensory abnormality but not CPSP, and those with no sensory abnormality. These groups were compared for sex, age at onset of stroke and at follow-up, stroke location, lesion size, and subtype of stroke (Trial of Org 10172 in Acute Stroke Treatment [TOAST]),16 history of recurrent ischemic stroke, and quality of life at follow-up. Location of stroke was defined as anterior, posterior, or both territories. We categorized lesion size as follows: (1) small, i.e., ,1.5 cm lesion in anterior or posterior circulation; (2) medium, i.e., lesion in a cortical superficial branch of the anterior cerebral artery, middle cerebral artery (MCA), or 1148
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posterior cerebral artery (PCA), or deep branch of MCA or PCA, or in internal border-zone territories; (3) large anterior, i.e., lesion involving complete territory of anterior cerebral artery or MCA, 2 branches of MCA, or .1 artery territory; and (4) large posterior, i.e., lesion .1.5 cm, involving brainstem, cerebellum, or entire territory of PCA including border-zone territories.17
Standard protocol approvals, registrations, and patient consents. The local ethics committee approved the study, and all participating patients gave their written informed consent.
Statistical analyses. The data are presented as means with SDs, medians with interquartile ranges, or counts with percentages. Pairwise comparisons between the 3 clinical subgroups were performed using x2, Fisher exact, and Mann–Whitney U tests, when appropriate. Logistic regression analysis with backward stepwise algorithm was constructed to study baseline factors associated with the occurrence of CPSP. Here, patients with CPSP were separately compared with (1) those with sensory abnormality but not CPSP, and (2) those with no sensory abnormality. Age and sex were forced in the models and variables significant in the univariate comparisons were then entered in the models. All analyses used SPSS 20 for Macintosh (IBM Inc., Armonk, NY). A 2tailed p value .0.05 was considered significant.
The median follow-up time from the stroke was 8.5 years (interquartile range 5.0–12.1), with longer follow-up time for patients without CPSP (9.3 years for those with sensory abnormality and 8.3 years for those without). Of the included 824 patients, 49 patients (5.9%) had CPSP, 246 (29.9%) had sensory abnormality without CPSP, and 529 (64.2%) had no sensory abnormality (figure 1). There was no difference in age at stroke onset or at follow-up, or subtype of stroke according to the TOAST classification between the groups. Compared with both comparator groups, strokes were more severe when measured with the NIHSS score among patients with CPSP. Regarding stroke territory, laterality, or anatomical distribution, no differences were found between the groups. However, lesions were larger and hemorrhagic transformation of the infarction occurred more often in patients with CPSP compared with those without CPSP or those with any sensory abnormality. After adjustment for NIHSS score, no significant correlation between hemorrhagic transformation and CPSP remained (odds ratio 1.78, 95% confidence interval 0.74–4.28; p 5 0.195). Quality of life was worse in patients with CPSP compared with both comparator groups (table). In the logistic regression analysis (adjusted for age, sex, and hemorrhagic transformation) comparing patients with CPSP to patients without any sensory abnormality, moderate (odds ratio 4.94, 95% confidence interval 2.3–10.45; p , 0.001) and severe (5.36, 2.21–12.96; p , 0.001) symptoms were associated with the occurrence of CPSP. In a similar analysis in which patients with CPSP were compared to those with sensory abnormality without CPSP (adjusted for age and sex), severe symptoms
RESULTS
Figure 1
Study population flowchart
CPSP 5 central poststroke pain.
(measured using the NIHSS) were associated more with CPSP (2.51, 1.01–6.23; p 5 0.047). Of the patients with CPSP, 31 (63%) were independent in their ADL, 17 (35%) needed partial
assistance, and 1 (2%) needed full assistance. Mobility was normal in 25 (51%), whereas 21 (43%) needed a cane or crutches, and 3 (6%) needed a wheelchair. Twelve (24%) of them were working full Neurology 83
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Table
Univariate comparison of patients with (1) neither sensory abnormality nor CPSP, (2) with sensory abnormality but without CPSP, and (3) with CPSP
All (N 5 824)
No sensory abnormality, no CPSP (n 5 529)
CPSP (n 5 49)
p for CPSP vs no sensory abnormality, no CPSP
Female sex
325 (39.4)
205 (38.8)
98 (39.8)
22 (44.9)
0.399
Age at stroke onset, y
40.7 (7.8)
40.2 (8.2)
41.5 (7.1)
41.3 (7.3)
0.503
NIHSS score
Sensory abnormality, no CPSP (n 5 246)
3 (1–5)
2 (1–4)
3 (2–8)
4 (3–12)
0–6 (mild)
677 (82.2)
466 (88.1)
182 (74.0)
29 (59.2)
7–14 (moderate)
95 (11.5)
39 (7.4)
44 (17.9)
12 (24.5)
‡15 (severe)
52 (6.3)
24 (4.5)
20 (8.1)
8 (16.3)
Lesion size Small
377 (45.8)
248 (46.9)
110 (44.7)
Moderate
240 (29.1)
171 (32.3)
60 (24.4)
9 (18.4)
Large posterior
97 (11.8)
64 (12.1)
28 (11.4)
5 (10.2)
Large anterior
110 (13.3)
46 (8.7)
48 (19.5)
16 (32.7)
Anterior
413 (50.1)
255 (48.2)
131 (53.3)
27 (55.1)
Posterior
379 (46.0)
255 (48.2)
103 (41.9)
21 (42.9)
Both
32 (3.9)
19 (3.6)
12 (4.9)
1 (2.0)
Lateralityb 355 (44.8)
222 (43.4)
111 (46.8)
0.510 0.658 a
,0.001
0.004a
,0.001a
0.234
0.601
0.676
0.186
0.343
19 (38.8)
Territory
Right
p for CPSP vs sensory abnormality, no CPSP
22 (48.9)
Left
362 (45.6)
234 (45.8)
106 (44.7)
22 (48.9)
Both
76 (9.6)
55 (10.8)
20 (8.4)
1 (2.2)
333 (40.4)
202 (38.2)
108 (43.9)
23 (46.9)
0.229
0.696
Anatomical location Cortical Subcortical
386 (46.8)
239 (45.2)
118 (48.0)
29 (59.2)
0.060
0.152
Thalamus
92 (11.2)
63 (11.9)
24 (9.8)
5 (10.2)
0.723
1.000
Basal ganglia
187 (22.7)
117 (22.1)
60 (24.4)
10 (20.4)
0.782
0.550
Cerebellum or brainstem
262 (31.8)
172 (32.5)
78 (31.7)
12 (24.5)
0.249
0.316
81 (9.8)
38 (7.2)
35 (14.2)
8 (16.3)
0.046a
0.704
0.866
0.939
Hemorrhagic transformation TOAST subgroup LAA
47 (5.7)
26 (4.9)
17 (6.9)
4 (8.2)
CE
160 (19.4)
105 (19.8)
44 (17.9)
11 (22.4)
SVO
111 (13.5)
69 (13.0)
36 (14.6)
6 (12.2)
OTH
219 (26.6)
142 (26.8)
65 (26.4)
12 (24.5)
UND
287 (34.8)
187 (35.3)
84 (34.1)
16 (32.7)
49.2 (9.1)
48.5 (9.3)
50.6 (8.4)
49.3 (8.8)
Age at follow-up, y EuroQoL VAS
80 (68–88)
80 (70–90)
75 (60–80)
70 (50–80)
0.749
0.360 a
,0.001
0.007a
Abbreviations: CE 5 cardioembolism; CPSP 5 central poststroke pain; LAA 5 large-artery atherosclerosis; NIHSS 5 NIH Stroke Scale; OTH 5 other determined etiology; SVO 5 small-vessel occlusion; TOAST 5 Trial of Org in Acute Stroke Treatment; UND 5 undetermined etiology; VAS 5 visual analog scale. Data are mean (SD), median (interquartile range), or n (%). a Significant values. b Thirty-one brainstem lesions were unclassifiable.
time, 2 (4%) were working part time, and 35 (71%) were retired. The onset of CPSP was between the first week and the first month after stroke in most cases (figure 2). 1150
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In patients with CPSP, the mean (SD) pain intensity in BPI was 5.3 (2.0) and the pain interference was 4.5 (2.7). Ten (20%) of the patients with CPSP rated their pain as mild, 26 (53%) moderate, 11 (22%) severe,
Figure 2
Onset of CPSP from stroke
Temporal distribution of the onset point of central poststroke pain (CPSP) from stroke.
and 2 (4%) as excruciating. Pain interference was graded as minimal by 3 patients (6%), mild by 14 patients (29%), moderate by 21 patients (43%), severe by 7 patients (14%), and very severe by 3 patients (6%). The mean (SD) Beck depression score in patients with CPSP was 11.5 (9.2), suggesting mild depression. Of the 49 patients with CPSP, 30 (61%) rated pain as their worst health problem. Nine patients (18%) named other neurologic symptoms (motor paresis, fatigue, visual disturbances), 3 patients (6%) depression or anxiety, and 7 patients (14%) any other symptom as their worst health problem. In addition to CPSP, 40 patients (82%) experienced other pain: musculoskeletal pain unrelated to stroke (10 patients), primary headache (5 patients), painful polyneuropathy (3 patients), and other stroke-associated non-CPSP pain (22 patients). Of the 22 patients, 8 had spasticity-related pain, 9 had joint pain, 4 had both spasticity-related and joint pain, and 1 had postcraniectomy headache. Of those who had CPSP and concomitant other pain, 26 (65%) regarded CPSP as their worst pain. In addition, another 130 of the 824 stroke patients (16%) reported non-CPSP pain, i.e., joint pain, back pain, headache, polyneuropathy. Twenty-eight (57%) of the patients with CPSP used regular pain medication: simple analgesics (24 patients), mild opioids (10 patients), gabapentinoids (8 patients), amitriptyline (2 patients), and lamotrigine (1 patient). None of the patients were on strong opioids. A total of 31 patients with moderate or severe CPSP did not use neuropathic pain medication. Eight of them had tried neuropathic pain medications, but abandoned the medication because of adverse effects and/or unsatisfactory pain relief.
PainDETECT questionnaire was adequately completed by 48 patients with CPSP. The current pain intensity was 5 (mean) (SD 2.2), the worst pain and the mean pain during the previous 30 days were 8 (1.9) and 5.5 (1.8), respectively. Pain was in most cases continuous with several worsening attacks in between (46%). Only 15% of the patients (7 of 48) reported radiating pain. The mean (SD) PainDETECT score was 17 (5.7) and it was $19 in 35% of the patients (17 of 48 patients). The pain and sensory symptoms that scored higher than 3 (strong or very strong) were tingling pain (26 of 48 patients, 54%), electric shocks (14 of 48, 29%), and warm or cold allodynia (14 of 48, 29%). Numbness was scored strong or very strong by 46% of patients (22 of 48). In the sensory examination, hypoesthesia to warm was found in 29 patients (62%), to cold in 20 (43%), to pinprick in 13 (28%), and to touch in 11 patients (23%). Hyperesthesia to pinprick was found in 17 (36%), to cold in 6 (13%), and to warm in 6 (13%). Dysesthesia was present to touch in 30 patients (62%), to cold in 5 (11%), and to warm in 4 patients (9%). Dynamic mechanical allodynia was found in 10 (21%) and static mechanical allodynia in 7 patients (15%). Of the sensory abnormalities, hypoesthesia was found in 10 (21%), hyperesthesia or allodynia in 11 (23%), and a combination of them as the most frequent finding in 26 patients (55%). Any kind of allodynia was found in 21 patients (45%) with CPSP: cold allodynia was the most frequent in 14 patients (29%), warm allodynia in 5 (10%), and mechanical allodynia in 2 patients (4%). In this large, well-defined cohort of consecutive young ischemic stroke survivors, the occurrence of CPSP was 5.9%. Severe strokes with hemorrhagic transformation were more likely to associate with CPSP. The anatomical localization of stroke was diverse to cause CPSP. Moreover, patients with CPSP had worse quality of life than patients in comparator groups. Most of the patients had survived well from stroke with most of them independent in their ADL and mobility, but the majority were on retirement. Most patients with CPSP reported moderate pain, mild depression, and reduced quality of life. Our CPSP rate of 5.9% is in accordance with 2 Danish population-based studies of older age groups.1,4 According to the replies to the postal questionnaire, 30% of the stroke survivors had a subjective sensory abnormality without CPSP in our study (figure 1). Based on the CPSP classification,3,18 42 of our patients had definite and 7 had probable CPSP. Four patients with probable CPSP had no findings in neuroimaging and 2 had not been clinically examined, but had an ischemic lesion in brain CT or DISCUSSION
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Figure 3
Pain drawings of patients with central poststroke pain (CPSP)
The patients drew pain areas; those marked in gray are located in the back of the body.
MRI,8 both valid for detecting ischemic and hemorrhagic lesions. In sensory examination, all but one of the examined patients had abnormal findings compatible with a lesion of the somatosensory system and with their body pain areas (figure 3). Central pain, including CPSP, may arise from an imbalance of facilitatory and inhibitory systems that include interactions among the spinal cord, the nuclei of the brainstem, and supraspinal thalamocortical circuits.2 Thus, various kinds of stroke lesions may cause 1152
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CPSP. However, in some studies, lateral medullary infarction or lesions in the ventroposterior part of the thalamus were related to a high prevalence of CPSP (25% and 18%, respectively).19,20 In our study, there was no correlation regarding stroke localization. However, stroke severity with hemorrhagic transformation correlated with the presence of CPSP. A previous study has also reported a correlation between hemorrhagic transformation and CPSP. In that study, many of the lesions were thalamic, which was considered the most likely cause of CPSP.21 Our study suggests a risk of developing CPSP if a young stroke patient has a large ischemic lesion with hemorrhagic transformation. Nevertheless, with our sample size, hemorrhagic transformation did not remain as an independently associated risk factor for developing CPSP. A large study on chronic pain syndromes after ischemic stroke (Prevention Regimen for Effectively avoiding Second Stroke [PRoFESS] Trial) reported that 431 of 15,754 patients had CPSP (2.7%), a prevalence lower than ours.22 Younger age and stroke severity were significant predictors for CPSP, in line with our findings. Some type of allodynia occurred in 45% of our patients with CPSP. An even higher prevalence of allodynia (71%) has been reported.6 Cold allodynia, pinprick hyperalgesia, and dysesthesia in response to touch were common findings in our study and in line with a previous finding.1 Cold allodynia was by far the most common type of allodynia in our series. In accordance with previous reports, CPSP appeared during the first month after stroke in most cases,4 was at least of moderate intensity in most patients, and interfered at least moderately with daily life in most patients.1 Our patients with CPSP had lower quality of life than stroke survivors without CPSP, in line with a previous report.23 PainDETECT has previously been used for identifying different sensory profiles of peripheral neuropathic pain, such as postherpetic neuralgia and painful diabetic neuropathy.24 It has not previously been used to define CPSP. Tingling or electric shocklike pain, cold or warm allodynia, and numbness were the most common descriptors of pain in PainDETECT in our patients with CPSP. This is in line with the 7-item Douleur Neuropathique 4 questionnaire25 that was used in a previous CPSP study.26 However, it remains uncertain whether PainDETECT as such is useful as a screening tool for CPSP. In our study, the mean points in PainDETECT were moderate (17). The sum of scores $19 indicates that neuropathic pain is likely. Originally, the PainDETECT validation was performed for patients with chronic low back pain. In PainDETECT, the patient receives 2 additional scores if there is radiating pain. This is logical for neuropathic
type of low back pain, but, according to our study, not useful for CPSP. A modified PainDETECT could be developed for central neuropathic pain with additional scores if the patient reports tingling or electric shocktype pain, or warm or cold allodynia. Patients with CPSP frequently experience concomitant musculoskeletal pain,1,2,27 which was the case in most of our patients with CPSP as well. Most of our patients receiving pain treatment used simple analgesics, whereas the use of neuropathic pain medication was less common. This may reflect underuse of appropriate analgesics, insufficient response to neuropathic pain treatment, intolerable side effects, or underuse of medication. Only 26% of our patients with CPSP with moderate or severe pain had ever been offered neuropathic pain medications, which may reflect the underdiagnostics of CPSP. More emphasis should be applied to effective management of pain immediately after the diagnosis. However, CPSP can be rather resistant to pharmacologic management with drugs that are recommended for pain treatment of CPSP. Therefore, new approaches for difficult-to-treat central pain, e.g., transcranial magnetic stimulation, are needed.28–30 This study has some limitations. The clinical examination did not include quantitative sensory testing. However, to perform quantitative sensory testing in all of the patients with sensory abnormality (295 patients) would have been costly, not particularly feasible, and not required for definite CPSP diagnosis according to CPSP classification. Not all of our CPSP candidates attended clinical examination and 4 of them had no initial findings in neuroimaging. Brain MRI was not done in all patients and thus the lesion characterization relied on CT in some patients. Thus, volumetric studies of the stroke lesions could not be done. Strengths of our study are the large, virtually population-based cohort, meticulous clinical examination of the patients, and the use of the grading system for CPSP diagnosis. In a young stroke patient population, 1 of 17 developed CPSP. CPSP was more likely in stroke patients with a severe stroke regardless of sex and age and was often associated with other types of pain. Quality of life worsens with CPSP and pain may thus negatively affect acute and chronic stroke rehabilitation. AUTHOR CONTRIBUTIONS H.H. analyzed and interpreted the data, drafted the manuscript, and contributed to the scientific content. E.H. designed the study, collected data, examined patients, contributed to the scientific content, and revised the manuscript. J.P. designed the study, performed advanced statistical analyses of the data, interpreted the data, drafted the manuscript, and contributed to the scientific content. M.H. designed the study, drafted the manuscript, collected data, examined the patients, and contributed to the scientific content. J.P.M. contributed to the scientific content and revised the manuscript. E.K. contributed to the scientific content and revised the manuscript. T.T. designed and supervised the study, revised the manuscript, and contributed to the scientific content.
STUDY FUNDING Supported by the Helsinki University Central Hospital Research Funds.
DISCLOSURE The authors report no disclosures relevant to the manuscript. Go to Neurology.org for full disclosures.
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Central poststroke pain in young ischemic stroke survivors in the Helsinki Young Stroke Registry Hanna Harno, Elena Haapaniemi, Jukka Putaala, et al. Neurology 2014;83;1147-1154 Published Online before print August 15, 2014 DOI 10.1212/WNL.0000000000000818 This information is current as of August 15, 2014 Updated Information & Services
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References
This article cites 28 articles, 9 of which you can access for free at: http://www.neurology.org/content/83/13/1147.full.html##ref-list-1
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