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This study aimed to assess occurrence and significance of postoperative neuropathic pain in patients with surgically-treated brainstem cavernous malformations (BSCM).
Seventy-four BSCM patients surgically treated between 2003 and 2019 were reviewed for the occurrence of postoperative NP and related treatment. We evaluated relevance of BSCM location, preoperative characteristics, influence on functional outcome, postoperative health-related quality of life (HRQOL), and life satisfaction (LS).
Six out of 74 patients (8%) suffered from NP. Leeds Assessment of Neuropathic Symptoms and Signs scores (LANSS) ranged from 12-16 (mean 14.28 ± 1.6). Visual analog scale pain was 5.2 ± 2.0. NP had no effect on preoperative characteristics or functional outcome. Bodily pain (HRQOL) and vocational time (LS) were significantly decreased in NP compared to non-NP patients. Specific BSCM location (regarding brainstem nuclei involved in pain processing) and other preoperative patient-and BSCM-related parameters were not associated with the occurrence of postoperative NP. Three out of 6 patients were currently under NP-specific treatment. The proportion of patients suffering from postoperative NP (8%) was substantially higher as compared to previously published studies. The pain affected the HRQOL of patients, most of whom were insufficiently treated and not satisfied with treatment results.
Our findings may help raising awareness for postoperative NP in BSCM, which is essential to improve diagnosis and initiation of proper treatment, as well as preoperative informed consent of patients.
To estimate health related quality of life (HRQOL) in patients with untreated cavernous malformation of the CNS (CCM).
We performed a cross-sectional observational study on patients with CCM admitted to our department from 01.11.2017-10.01.2020 using standardized interviews (short-form -36 questionnaire, hospital anxiety and depression score (HADS-A/D), CCM-perception questionnaire). Including criteria was diagnosis of an untreated CCM and information about the diagnosis in a specialized CCM consultation. HRQOL data was analyzed and compared to German normal population. Uni- and multivariate analyses were carried out to identify variables with impact on outcome.
219 (93%) of 229 eligible patients were included. Mean age was 46.3 ±14.7 (18-86) years, 136 (62%) were female. 98 (45%) patients presented with symptomatic hemorrhage and 17 (8%) with repetitive SH. 92 (42%) patients were asymptomatic. 37 (17%) suffered from cavernoma-related epilepsy. 28 patients (13%) suffered from familial CCM. Patients showed significantly decreased component scores and subdomain scores compared to normal population with effects ranging from small to large. This accounted largely also for asymptomatic patients (except for physical component score and main physical subdomains). Multivariate regression analysis confirmed impact of functional impairment on physical component score. HADS-A was significantly increased. HADS-A/D strongly correlated with mental component score and individual perception of the CCM.
Patients with the diagnosis of a CCM showed decreased HRQOL compared to normal population even when not suffering functional impairment or neurological symptoms. Our data may function as benchmark in evaluation of different (future) management strategies.
The brainstem is known to be an important brain area for nociception and pain processing, and both relaying and coordinating signaling between the cerebrum, cerebellum, and spinal cord. Although preclinical models of pain have characterized the many roles that brainstem nuclei play in nociceptive processing, the degree to which these circuitries extend to humans is not as well known. Unfortunately, the brainstem is also a very challenging region to evaluate in humans with neuroimaging. The challenges for human brainstem imaging arise from the location of this elongated brain structure, proximity to cardiorespiratory noise sources, and the size of its constituent nuclei. These challenges can require dedicated approaches to brainstem imaging, which should be adopted when study hypotheses are focused on brainstem processing of nociception or modulation of pain perception. In fact, our review will highlight many pain neuroimaging studies that have reported some brainstem involvement in nociceptive processing and chronic pain pathology. However, we note that with recent advances in neuroimaging leading to improved spatial and temporal resolution, more studies are needed that take advantage of data collection and analysis methods focused on the challenges of brainstem neuroimaging.
The objective of this review was to merge current treatment guidelines and best practice recommendations for management of neuropathic pain into a comprehensive algorithm for primary physicians. The algorithm covers assessment, multidisciplinary conservative care, nonopioid pharmacological management, interventional therapies, neurostimulation, low-dose opioid treatment, and targeted drug delivery therapy.
Available literature was identified through a search of the US National Library of Medicine's Medline database, PubMed.gov. References from identified published articles also were reviewed for relevant citations.
The algorithm provides a comprehensive treatment pathway from assessment to the provision of first- through sixth-line therapies for primary care physicians. Clear indicators for progression of therapy from firstline to sixth-line are provided. Multidisciplinary conservative care and nonopioid medications (tricyclic antidepressants, serotonin norepinephrine reuptake inhibitors, gabapentanoids, topicals, and transdermal substances) are recommended as firstline therapy; combination therapy (firstline medications) and tramadol and tapentadol are recommended as secondline; serotonin-specific reuptake inhibitors/anticonvulsants/NMDA antagonists and interventional therapies as third-line; neurostimulation as a fourth-line treatment; low-dose opioids (no greater than 90 morphine equivalent units) are fifth-line; and finally, targeted drug delivery is the last-line therapy for patients with refractory pain.
The presented treatment algorithm provides clear-cut tools for the assessment and treatment of neuropathic pain based on international guidelines, published data, and best practice recommendations. It defines the benefits and limitations of the current treatments at our disposal. Additionally, it provides an easy-to-follow visual guide of the recommended steps in the algorithm for primary care and family practitioners to utilize.
Physical, psychological, and/or social impairment can result after a stroke and can be exacerbated by pain. One type of pain after stroke, central poststroke pain, is believed to be due to primary central nervous system mechanisms. Estimated prevalence of central poststroke pain ranges widely from 8% to 55% of stroke patients, suggesting a difficulty in reliably, accurately, and consistently identifying central poststroke pain. This may be due to the absence of a generally accepted definition.
We aimed to clarify the role of thalamic strokes and damage to the spinothalamic pathway in central poststroke pain patients. Also, we aimed to gain a current understanding of anatomic substrates, brain imaging, and treatment of central poststroke pain.
Summary of review
Two independent reviewers identified 10,144 publications. Based on Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines, we extracted data from 23 papers and categorized the articles’ aims into four sections: somatosensory deficits, pathway stimulation, clinical trials, and brain imaging.
Our systematic review suggests that damage to the spinothalamic pathway is associated with central poststroke pain and this link could provide insights into mechanisms and treatment. Moreover, historical connection of strokes in the thalamic region of the brain and central poststroke pain should be reevaluated as many studies noted that strokes in other regions of the brain have high occurrence of central poststroke pain as well.
Pain following stroke is commonly reported but often incompletely managed, which prevents optimal recovery. This is in part due to the esoteric nature of post-stroke pain and its limited presence in current discussions of stroke management. The major specific afflictions that affect patients with stroke who develop pain include central post-stroke pain (CPSP), complex regional pain syndrome (CRPS), and pain associated with spasticity and shoulder subluxation. Each disorder carries its own intricacies that require specific approaches to treatment and understanding. This review aims to present and clarify the major pain syndromes that affect patients who have suffered from stroke in order to aid in their diagnosis and treatment.
Cerebral cavernous malformations are the most common vascular malformations and can be found in many locations in the brain. If left untreated, cavernomas may lead to intracerebral hemorrhage, seizures, focal neurological deficits, or headaches. As they are angiographically occult, their diagnosis relies on various MR imaging techniques, which detect different characteristics of the lesions as well as aiding in planning the surgical treatment. The clinical presentation and the location of the lesion are the most important factors involved in determining the optimal course of treatment of cavernomas. We concisely review the literature and discuss the advantages and limitations of each of the three available methods of treatment-microsurgical resection, stereotactic radiosurgery, and conservative management-depending on the lesion characteristics.
To characterize neuropathic pain in patients with spinal cord injury (SCI) according to classification used in the study by Baron et al. (Baron classification), a classification of neuropathic pain based on the mechanism. To also compare the patterns of neuropathic pain in SCI patients with those in patients with other etiologies and to determine the differences in patterns of neuropathic pain between the etiologies.
This was a descriptive cross-sectional study. We used the Baron classification to investigate the characteristics of neuropathic pain in SCI. Sixty-one SCI patients with neuropathic pain (The Leeds assessment of neuropathic symptoms and signs score ≥12) were enrolled in this study between November 2012 and August 2013, after excluding patients <20 of age, patients with visual analog scale (VAS) score <3, pregnant patients, and patients with systemic disease or pain other than neuropathic pain.
The most common pain characteristic was pricking pain followed by electrical pain and numbness. The mean VAS score of at-level neuropathic pain was 7.51 and that of below-level neuropathic pain was 6.83. All of the patients suffered from rest pain, but 18 (54.6%) patients with at-level neuropathic pain and 20 (50.0%) patients with below-level neuropathic pain suffered from evoked pain. There was no significant difference in between at-level and below-level neuropathic pains.
The result was quite different from the characteristics of post-herpetic neuralgia, but it was similar to the characteristics of diabetic neuropathy as shown in the study by Baron et al., which means that sensory nerve deafferentation may be the most common pathophysiologic mechanism of neuropathic pain after SCI. Since in our study, we included short and discrete symptoms and signs based on diverse mechanisms, our results could be helpful for determining further evaluation and treatment.
Cavernous malformations (CMs) consist of dilated vascular channels that have a characteristic appearance on MRI. CMs are usually found intracranially, although such lesions can also affect the spinal cord. Individuals with CMs can present with epilepsy and focal neurological deficits or acute intracranial hemorrhage. In many cases, however, patients with such lesions are asymptomatic at diagnosis. Furthermore, several natural history studies have documented that a substantial proportion of asymptomatic CMs follow a benign course. Surgical resection is recommended for CMs that require intervention. Radiosurgery has been advocated for many lesions that have not been easily accessible by conventional surgery. The outcomes of radiosurgery and surgery for deep lesions, however, vary widely between studies, rendering treatment recommendations for such CMs difficult to make. In addition to reviewing the literature, this article will discuss the current understanding of lesion pathophysiology and explore the controversial issues in the management of CMs, such as when to use radiosurgery or surgery in deep-seated lesions, the treatment of epilepsy, and the safety of anticoagulation.
This study describes the development and validation of a novel tool for identifying patients in whom neuropathic mechanisms dominate their pain experience. The Leeds assessment of neuropathic symptoms and signs (LANSS) Pain Scale is based on analysis of sensory description and bedside examination of sensory dysfunction, and provides immediate information in clinical settings. It was developed in two populations of chronic pain patients. In the first (n = 60), the use of sensory descriptors and questions were compared in patients with nociceptive and neuropathic pain, combined with an assessment of sensory function. This data was used to derive a seven item pain scale, consisting of grouped sensory description and sensory examination with a simple scoring system. The LANSS Pain Scale was validated in a second group of patients (n = 40) by assessing discriminant ability, internal consistency and agreement by independent raters. Clinical and research applications of the LANSS Pain Scale are discussed.
OBJECTIVE: The object of this study was to assess outcome after surgery for brainstem cavernous malformations (BSCMs) using functional, health-related quality of life (HRQOL), and psychological surveys to analyze the interrelation of these measurements, and to compare HRQOL and anxiety and depression scores with those in a healthy population.
METHODS: The authors performed a cross-sectional outcome study of all patients surgically treated for BSCM in their department between January 1, 2003, and December 31, 2019. They assessed functional outcome via the modified Rankin Scale (mRS), health-related quality of life (HRQOL) via the SF-36 and 9-item Life Satisfaction Questionnaire (LISAT-9), cranial nerve and brainstem function using a questionnaire, symptom-based psychological outcome via the Hospital Anxiety and Depression Scale (HADS), and timepoint of a return to previous employment. They analyzed the correlation between absolute (mRS score ≤ 2) and relative (postoperative deterioration in initial mRS score) outcome endpoints and the interrelation of the outcome measures and performed a comparison of HRQOL and HADS scores with findings in a healthy population.
RESULTS: Seventy-four patients were eligible for inclusion in the study. HRQOL was impaired after surgery for BSCM compared to that in a healthy population. This impairment was substantial in patients with an unfavorable functional out-come (mRS > 2) but was also present in those with a favorable outcome (mRS ≤ 2) in selected domains. Psychological impairment was negligible in patients with a favorable outcome and grave in those with an unfavorable outcome. LISAT-9 results revealed that brainstem and cranial nerve symptoms reduce satisfaction mainly in self-care abilities for both unfa- vorable and favorable outcome patients. Among the brainstem and cranial nerve symptoms, balance impairment showed the most significant impact on HRQOL. Absolute outcome endpoints were superior to relative outcome endpoints in reflecting impairment in HRQOL after surgery.
CONCLUSIONS: The study data can improve patient counseling and decision-making in BSCM treatment and may function as a benchmark. The authors report outcomes after BSCM surgery in high detail, emphasizing the specific impact of cranial nerve and brainstem symptoms on HRQOL. When reporting BSCM surgery outcome, absolute out-come endpoints should be applied.
Given the paucity of data on the natural history of brainstem cavernous malformations (CMs), the authors aimed to evaluate the annual hemorrhage rate and hemorrhagic risk of brainstem CMs.
Nine hundred seventy-nine patients diagnosed with brainstem CMs were referred to Beijing Tiantan Hospital from 2006 to 2015; 224 patients were excluded according to exclusion criteria, and 47 patients were lost to follow-up. Thus, this prospective observational cohort included 708 cases (324 females). All patients were registered, clinical data were recorded, and follow-up was completed.
Six hundred ninety (97.5%) of the 708 patients had a prior hemorrhage, 514 (72.6%) had hemorrhagic presentation, and developmental venous anomaly (DVA) was observed in 241 cases (34.0%). Two hundred thirty-seven prospective hemorrhages occurred in 175 patients (24.7%) during 3400.2 total patient-years, yielding a prospective annual hemorrhage rate of 7.0% (95% CI 6.2%-7.9%), which decreased to 4.7% after the 1st year. Multivariate Cox regression analysis after adjusting for sex and age identified hemorrhagic presentation (HR 1.574, p = 0.022), DVA (HR 1.678, p = 0.001), mRS score ≥ 2 on admission (HR 1.379, p = 0.044), lesion size > 1.5 cm (HR 1.458, p = 0.026), crossing the axial midpoint (HR 1.446, p = 0.029), and superficially seated location (HR 1.307, p = 0.025) as independent adverse factors for prospective hemorrhage, but history of prior hemorrhage was not significant. The annual hemorrhage rates were 8.3% and 4.3% in patients with and without hemorrhagic presentation, respectively; the rate was 9.9%, 6.0%, and 1.0% in patients with ≥ 2, only 1, and 0 prior hemorrhages, respectively; and the rate was 9.2% in patients with both hemorrhagic presentation and focal neurological deficit on admission.
The study reported an annual hemorrhage rate of 7.0% exclusively for brainstem CMs, which significantly increased if patients presented with both hemorrhagic presentation and focal neurological deficit (9.2%), or any other risk factor. Patients with a risk factor for hemorrhage needed close follow-up regardless of the number of prior hemorrhages. It should be noted that the referral bias in this study could have overestimated the annual hemorrhage rate. This study improved the understanding of the natural history of brainstem CMs, and the results are important for helping patients and physicians choose a suitable treatment option based on the risk factors and stratified annual rates.Clinical trial registration no.: ChiCTR-POC-17011575 (http://www.chictr.org.cn/).
Background and Purpose—
The goal of this study was to systematically review the outcomes and complications after surgical resection of brain stem cavernous malformations (BCMs).
A systematic literature review was performed using the PubMed database for studies published between 1986 and 2018. All studies comprising ≥2 patients with surgically resected BCMs and available follow-up data were included. Data extracted from studies included patient demographics, BCM location, and surgical outcomes.
Eighty-six studies comprising 2493 patients (adult and pediatric) were included for final analysis. Complete resection was achieved in 92.3% (fixed-effects pooled estimate [FE], 92.9% [91.7%–94.0%]; random-effects pooled estimate [RE], 89.4% [86.5%–92.0%]) of patients, and rehemorrhage of residual BCMs occurred in 58.6% (FE, 58.8% [49.7%–67.6%]; RE, 57.2% [43.5%–70.2%]). Postoperative morbidity occurred in 34.8% (FE, 30.9% [29.0%–32.8%]; RE, 31.1% [25.8%–36.6%]) of patients. Postoperative morbidities included motor deficit in 11.0% (FE, 9.9% [8.1%–11.7%]; RE, 11.1% [7.0%–16.0%]), sensory deficit in 6.7% (FE, 6.3% [4.8%–7.9%]; RE, 7.6% [4.5%–11.5%]), tracheostomy/gastrostomy in 6.0% (FE, 5.2% [4.3%–6.1%]; RE, 3.8% [2.6%–5.3%]), and other cranial nerve deficits in 29.4% (FE, 27.6% [25.3%–29.9%]; RE, 33.9% [25.7%–42.6%]) of patients. At final follow-up, 57.9% (FE, 57.6% [55.6%–59.6%]; RE, 57.2% [52.1%–62.3%]) and 25.9% (FE, 24.1% [22.4%–25.9%]; RE, 18.5% [14.6%–22.8%]) of patients had improvement and stability of preoperative symptoms, respectively. Mortality rate was 1.6% (FE, 1.9% [1.4%–2.5%]; RE, 1.8% [1.4%–2.5%]).
High cure rates and low rates of postoperative morbidity can be achieved with surgery in patients with BCMs. Most patients had improved preoperative symptoms at final follow-up. To avoid rehemorrhage, complete resection should be the goal of surgery.
Despite many publications about cerebral cavernous malformations (CCMs), controversy remains regarding diagnostic and management strategies.
To develop guidelines for CCM management.
The Angioma Alliance ( www.angioma.org ), the patient support group in the United States advocating on behalf of patients and research in CCM, convened a multidisciplinary writing group comprising expert CCM clinicians to help summarize the existing literature related to the clinical care of CCM, focusing on 5 topics: (1) epidemiology and natural history, (2) genetic testing and counseling, (3) diagnostic criteria and radiology standards, (4) neurosurgical considerations, and (5) neurological considerations. The group reviewed literature, rated evidence, developed recommendations, and established consensus, controversies, and knowledge gaps according to a prespecified protocol.
Of 1270 publications published between January 1, 1983 and September 31, 2014, we selected 98 based on methodological criteria, and identified 38 additional recent or relevant publications. Topic authors used these publications to summarize current knowledge and arrive at 23 consensus management recommendations, which we rated by class (size of effect) and level (estimate of certainty) according to the American Heart Association/American Stroke Association criteria. No recommendation was level A (because of the absence of randomized controlled trials), 11 (48%) were level B, and 12 (52%) were level C. Recommendations were class I in 8 (35%), class II in 10 (43%), and class III in 5 (22%).
Current evidence supports recommendations for the management of CCM, but their generally low levels and classes mandate further research to better inform clinical practice and update these recommendations. The complete recommendations document, including the criteria for selecting reference citations, a more detailed justification of the respective recommendations, and a summary of controversies and knowledge gaps, was similarly peer reviewed and is available on line [ www.angioma.org/CCMGuidelines ].
To quantify the risk of a first or recurrent hemorrhage and the associated functional impairment in patients with sporadic solitary cerebral cavernous malformations (CCM) and investigate the potential risk factors.
We undertook an observational study (n=199) of consecutive patients with the diagnosis of a single, sporadic CCM using clinical and MRI follow-up to identify prospective hemorrhage events and associated functional impairment. We calculated the annual hemorrhage risk rates, cumulative risks and performed uni- and multivariate analysis to assess outcome predictors.
199 adults were identified and 712.5 person-years of follow-up were analyzed. Overall annual rates of hemorrhage were 6.03%, 11.95% and 1.03% in the complete cohort, in those presenting with previous hemorrhage and in those without, respectively. The 5-year risk of hemorrhage was higher in those presenting with previous hemorrhage compared to those without (40.9% (95% CI 31.78 - 50.73) vs. 8.6% (3.97 - 16.95); p<0.0001) and in those with a brainstem-CCM compared to non-brainstem-CCM (51.6% (37.61 - 65.46) vs. 17.1% (4.55 - 32.04); p< 0.0001). In the multivariate analysis previous hemorrhage (odds ratio 7.18, 95% CI 1.8 - 28.11, p = 0.005), age <45 years (2.61, 1.03 - 6.61, p = 0.042) and brainstem location (7.44, 2.09 - 26.50, p = 0.002) increased the risk of hemorrhage. 30% of patients showed a moderate or severe disability associated with a CCM hemorrhage (5-year risk of "severe" hemorrhage 8.9% (95% CI 5.50 - 13.99)).
This study provides an estimate of symptomatic hemorrhage risk and the associated disability in patients with sporadic solitary CCM and an investigation of risk factors.
The redefinition of neuropathic pain as “pain arising as a direct consequence of a lesion or disease affecting the somatosensory system,” which was suggested by the International Association for the Study of Pain (IASP) Special Interest Group on Neuropathic Pain (NeuPSIG) in 2008, has been widely accepted. In contrast, the proposed grading system of possible, probable, and definite neuropathic pain from 2008 has been used to a lesser extent. Here, we report a citation analysis of the original NeuPSIG grading paper of 2008, followed by an analysis of its use by an expert panel and recommendations for an improved grading system. As of February, 2015, 608 eligible articles in Scopus cited the paper, 414 of which cited the neuropathic pain definition. Of 220 clinical studies citing the paper, 56 had used the grading system. The percentage using the grading system increased from 5% in 2009 to 30% in 2014. Obstacles to a wider use of the grading system were identified, including (1) questions about the relative significance of confirmatory tests, (2) the role of screening tools, and (3) uncertainties about what is considered a neuroanatomically plausible pain distribution. Here, we present a revised grading system with an adjusted order, better reflecting clinical practice, improvements in the specifications, and a word of caution that even the “definite” level of neuropathic pain does not always indicate causality. In addition, we add a table illustrating the area of pain and sensory abnormalities in common neuropathic pain conditions and propose areas for further research.
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.
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 = 58) with suspected CPSP were invited to a clinical visit and filled in the PainDETECT, Brief Pain Inventory, and Beck Depression Inventory questionnaires.
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 = 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.
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.
Information pertaining to the natural history of intramedullary spinal cord cavernous malformations (ISCCMs) and patient outcomes after surgery is scarce. To evaluate factors associated with favorable outcomes for patients with surgically and conservatively managed ISCCMs, the authors performed a systematic review and metaanalysis of the literature. In addition, they included their single-center series of ISCCMs.
The authors searched MEDLINE, EMBASE, CINAHL, Google Scholar, and The Cochrane Library for studies published through June 2013 that reported cases of ISCCMs. Data from all eligible studies were used to examine the epidemiology, clinical features, and neurological outcomes of patients with surgically managed and conservatively treated ISCCMs. To evaluate several variables as predictors of favorable neurological outcomes, the authors conducted a meta-analysis of individual patient data and performed univariate and multivariate logistic regression analyses. Variables included patient age, patient sex, lesion spinal level, lesion size, cerebral cavernomas, family history of cavernous malformations, clinical course, presenting symptoms, treatment strategy (operative or conservative), symptom duration, surgical approach, spinal location, and extent of resection. In addition, they performed a meta-analysis to determine a pooled estimate of the annual hemorrhage rate of ISCCMs.
Eligibility criteria were met by 40 studies, totaling 632 patients, including the authors' institutional series of 24 patients. Mean patient age was 39.1 years (range 2-80 years), and the male-to-female ratio was 1.1:1. Spinal levels of cavernomas were cervical (38%), cervicothoracic (2.4%), thoracic (55.2%), thoracolumbar (0.6%), lumbar (2.1%), and conus medullaris (1.7%). Average cavernoma size was 9.2 mm. Associated cerebral cavernomas occurred in 16.5% of patients, and a family history of cavernous malformation was found for 11.9% of evaluated patients. Clinical course was acute with stepwise progression for 45.4% of patients and slowly progressive for 54.6%. Symptoms were motor (60.5%), sensory (57.8%), pain (33.8%), bladder and/or bowel (23.6%), respiratory distress (0.5%), or absent (asymptomatic; 0.9%). The calculated pooled annual rate of hemorrhage was 2.1% (95% CI 1.3%-3.3%). Most (89.9%) patients underwent resection, and 10.1% underwent conservative management (observation). Outcomes were better for those who underwent resection than for those who underwent conservative management (OR 2.79, 95% CI 1.46-5.33, p = 0.002). A positive correlation with improved neurological outcomes was found for resection within 3 months of symptom onset (OR 2.11, 95% CI 1.31-3.41, p = 0.002), hemilaminectomy approach (OR 3.20, 95% CI 1.16-8.86, p = 0.03), and gross-total resection (OR 3.61, 95% CI 1.24-10.52, p = 0.02). Better outcomes were predicted by an acute clinical course (OR 1.72, 95% CI 1.10-2.68, p = 0.02) and motor symptoms (OR 1.76, 95% CI 1.08-2.86, p = 0.02); poor neurological recovery was predicted by sensory symptoms (OR 0.58, 95% CI 0.35-0.98, p = 0.04). Rates of neurological improvement after resection were no higher for patients with superficial ISCCMs than for those with deep-seated ISCCMs (OR 1.36, 95% CI 0.71-2.60, p = 0.36).
Intramedullary spinal cord cavernous malformations tend to be clinically progressive. The authors' findings support an operative management plan for patients with a symptomatic ISCCM. Surgical goals include gross-total resection through a more minimally invasive hemilaminectomy approach within 3 months of presentation.
International translation and psychometric testing of generic health outcome measures is increasingly in demand. Following the methodology developed by the International Quality of Life Assessment group (IQOLA) we report the German work with the SF-36 Health Survey. The form was translated using a forward-backward method with accompanying translation quality ratings and pilot tested in terms of translation clarity and applicability. Psychometric evaluation included Thurstone's test of ordinality and equidistance of response choices in 48 subjects as well as testing of reliability, validity, responsiveness and discriminative power of the form in crossectional studies of two samples of healthy persons and longitudinal studies of two samples of pain patients totalling 940 respondents. Quality ratings of translations were favorable, suggesting a high quality of both forward and backward translations. In the pilot study, the form was well understood and easily administered, suggesting high clarity and applicability. Thurstone's test revealed ordinality (in over 90% of the cases) and rough equidistance of response choices also as compared to the American original. On item and scale level, missing data were low and descriptive statistics indicated acceptable distribution characteristics. In all samples studied, discriminative item validity was high (over 90% scaling successes) and Cronbach's α reliabilities were above the 0.70 criterion with exception of one scale. Furthermore convergent validity, responsiveness to treatment and discriminative power in distinguishing between healthy and ill respondents was present. The preliminary results suggest that the SF-36 Health Survey in its German form may be a valuable tool in epidemiological and clinical studies. However further work as concerns responsiveness and population based norms is necessary.
Although surgical resection of brainstem cavernous malformations (CM) has been reviewed, numerous large surgical series have been recently reported.
Eighteen new surgical series with 710 patients were found via a PubMed search, in addition to our previous meta-analysis. Complete excision, complications, and long-term outcome results were compiled across these series. They were then compared and subsequently combined with those of our previous report.
We combined results of 68 surgical series with 1390 patients, incorporating results from our previous meta-analysis. Across 61 series, 1178 of 1291 (91%) CMs were completely excised. Of 105 partially resected CMs with ample follow-up, 65 rebled (62%). Across 46 series providing information on early neurologic morbidity, the overall rate was 45%. Specifically, 12% of patients required tracheostomy and/or gastrostomy procedures. Overall long-term condition was improved in 62% of patients across 51 series. Across 60 series, overall long-term condition was improved or the same in 84% of patients, with worsening in the remaining 16%. The overall surgical and/or cavernoma related mortality rate for all 1390 patients was 1.5%. Notably, these results did not differ significantly between our initial review and the combined data from the subsequent 18 surgical series recently reported in the literature.
Surgical resection of brainstem CM continues to present a considerable challenge with resultant morbidity akin to another CM hemorrhage. We therefore prefer to offer surgery only to patients with at least one previous hemorrhage with CM pial representation. Appropriate patient counseling about expected early morbidity and the potential for long-term worsening is crucial.
The aim of this study was to present normative values for the Hospital Anxiety and Depression Scale (HADS).
A representative sample of the German general population (N=4410) was tested with the HADS.
Females are more anxious than males, and older subjects are more depressed than younger subjects. The mean scores for anxiety / depression are 4.4 / 4.8 (males) and 5.0 / 4.7 (females). Using the cut-off 8+, the percentages of elevated anxiety and depression in the total sample are 21 % and 23 %, respectively. Regression analyses proved a linear but not a curvilinear age trend of anxiety and depression. Percentile rank norms are given for anxiety, depression, and the HADS total score.
The regression coefficients allow the calculation of expected mean scores for each age and gender distribution of any sample of patients. HADS mean scores are better suited to describe the degree of anxiety and depression in patient samples compared to percentages of subjects with elevated values.
Brainstem cavernous malformations (BSCMs) are relatively uncommon, low-flow vascular lesions. Because of their relative rarity, relatively little data on their natural history and on the efficacy and durability of their treatment.
To evaluate the long-term durability of surgical treatment of BSCMs and to document patient outcomes and clinical complications.
The charts of all patients undergoing surgical treatment of BSCM between 1985 and 2009 were reviewed retrospectively. The study population consisted of 300 patients who had surgery for BSCM. Forty patients were under 19 years of age at surgery; pediatric BSCMs have been reported separately. Patient demographics, lesion characteristics, surgical approaches, and patient outcomes were examined.
The study population consisted of 260 adult patients with a female-to-male ratio of 1.5 and mean age of 41.8 years. Of the 260 patients, 252 presented with a clinical or radiographic history of hemorrhage. The mean follow-up in 240 patients was 51 months. The mean Glasgow Outcome Scale on admission, at discharge, and at last follow-up was 4.4, 4.2, and 4.6. Postoperatively, 137 patients (53%) developed new or worsening neurological symptoms. Permanent new deficits remained in 93 patients 3(36%). There were perioperative complications in 74 patients (28%); tracheostomy, feeding tube placement, and cerebrospinal fluid leakage were most common. Eighteen patients (6.9%) experienced 20 rehemorrhages. Twelve patients required reoperation for residual/recurrent BSCM. The overall annual risk of postoperative rehemorrhage was 2%/patient.
Although BSCM surgery has significant associated risks, including perioperative complications, new neurological deficits, and death, most patients have favorable outcomes. Overall, surgery markedly improved the risk of rehemorrhage and related symptoms and should be considered in patients with accessible lesions.
Symptomatic patients with a brainstem cavernoma are treated surgically with increasing frequency. Generally, the patient's benefit from this difficult surgical intervention is quantified by the assessment of neurological symptoms.
To document the beneficial effect of surgery in a larger patient population by assessing the postoperative quality of life (QoL).
In a series of 71 surgically treated patients, a detailed neurological status was assessed by Patzold Rating and Karnofsky Performance Status Scale. Patients rated their QoL with the Short Form 36 Health Survey. To document the effect of surgery on QoL, we devised a supplementary questionnaire. The last 24 patients completed Short Form 36 Health Survey pre- and postoperatively.
Karnofsky Performance Status Scale improved in 44 of 71 surgical patients (62%), remained unchanged in 19 (27%), and deteriorated in 8 (11%) individuals. Patzold Rating showed a more detailed picture of the neurological symptoms. It correlated significantly with Karnofsky Performance Status Scale, which underscores its usefulness for patients with brainstem lesions. In the Short Form 36 Health Survey score, the Mental Component Summary improved with surgery (paired test, P = .015). In addition, 58 individuals (82%) declared a clear subjective benefit of surgery.
The results of this large series support the notion that microsurgical removal of a brainstem cavernoma represents an effective therapy in experienced hands and is generally associated with good clinical outcome, both neurologically and in terms of QoL.
Central poststroke pain (CPSP) is a specific pain condition arising as a direct consequence of a cerebrovascular lesion. There is limited knowledge about the epidemiology and clinical characteristics of this often neglected but important consequence of stroke. In this population-based study, a questionnaire was sent out to all (n=964) stroke patients identified through the Danish National Indicator Project Stroke Database in Aarhus County, Denmark, between March 2004 and February 2005. All surviving patients who fulfilled 4 questionnaire criteria for possible CPSP (n=51) were selected for further clinical examination, and their pain was classified by using stringent and well-defined criteria and a detailed, standardized clinical examination. The minimum prevalence of definite or probable CPSP in this population is 7.3% and the prevalence of CPSP-like dysesthesia or pain is 8.6%. Pinprick hyperalgesia was present in 57%, cold allodynia in 40%, and brush-evoked dysesthesia in 51% of patients with CPSP. Because of its negative impact on quality of life and rehabilitation, pain is an important symptom to assess in stroke survivors.
Although originally the subject of rare case reports, intramedullary spinal cord cavernous malformations (CMs) have recently surfaced in an increasing number of case series and natural history reports in the literature. The authors reviewed 27 publications with 352 patients to consolidate modern epidemiological, natural history, and clinical and surgical data to facilitate decision making when managing these challenging vascular malformations. The mean age at presentation was 42 years without a sex predilection. Thirty-eight percent of the cases were cervical, 57% thoracic, 4% lumbar, and 1% unspecified location. Nine percent of the patients had a family history of CNS CMs. Twenty-seven percent of the patients had an associated cranial CM. On presentation 63% of the patients had motor deficits, 65% had sensory deficits, 27% had pain, and 11% had bowel or bladder dysfunction. Presentation was acute in 30%, recurrent in 16%, and progressive in 54% of cases. An overall annual hemorrhage rate was calculated as 2.5% for 92 patients followed up for a total of 2571 patient-years. Across 24 reviewed surgical series, a 91% complete resection rate was found. Transient morbidity was seen in 36% of cases. Sixty-one percent of patients improved, 27% were unchanged, and 12% were worse at the long-term follow-up. Using this information, the authors review surgical nuances in treating these lesions and propose a management algorithm.
Central post-stroke pain (CPSP) is a neuropathic pain syndrome that can occur after a cerebrovascular accident. This syndrome is characterised by pain and sensory abnormalities in the body parts that correspond to the brain territory that has been injured by the cerebrovascular lesion. The presence of sensory loss and signs of hypersensitivity in the painful area in patients with CPSP might indicate the dual combination of deafferentation and the subsequent development of neuronal hyperexcitability. The exact prevalence of CPSP is not known, partly owing to the difficulty in distinguishing this syndrome from other pain types that can occur after stroke (such as shoulder pain, painful spasticity, persistent headache, and other musculoskeletal pain conditions). Future prospective studies with clear diagnostic criteria are essential for the proper collection and processing of epidemiological data. Although treatment of CPSP is difficult, the most effective approaches are those that target the increased neuronal hyperexcitability.
Brainstem cavernous malformations (CMs) continue to present a considerable source of controversy in the neurosurgical community, with an accumulating volume of literature detailing their natural history and their surgical and radiosurgical management. As part of a systematic review of the literature, 12 natural history studies, 52 surgical series, and 14 radiosurgical series were tabulated. Annual bleeding rates for brainstem CMs ranged from 2.3% to 4.1% in natural history studies and from 2.68% to 6.8% in surgical series before intervention. Rebleed rates as high as 21.5% in natural history studies and greater than once per year in surgical series were reported. A total of 684 of 745 CMs (92%) were documented as completely resected in 46 series that provided specific information on resection rates. Early postoperative morbidity ranged from 29% to 67% in larger surgical series, although it was often transient. Thirty of 61 partially resected lesions rebled; 4 of these rebleeds were fatal. Twelve additional patients died from surgically related causes for a combined postoperative rebleeding and surgically related mortality rate of 1.9%. Across 45 series (683 patients), 85% of patients were reported as the same or improved, 14% were worse, and 1.9% died from surgically related causes at long-term follow-up. Patients with anterolateral pontine lesions generally appeared to have a better functional recovery, whereas those requiring excision via the floor of the fourth ventricle had relatively worse long-term outcomes. Radiosurgical series demonstrated conflicting data; some reported a statistically significant decrease in CM rebleeding rates after 2 years, whereas others did not, partially related to dosimetry. Postradiosurgical morbidity was nonetheless significantly greater for CMs than for arteriovenous malformations.
Cavernous malformations of the brain (CMs) cause intracranial hemorrhage, but its reported frequency varies, partly attributable to study design. To improve the validity of future research, we aimed to develop a robust definition of CM hemorrhage.
We systematically reviewed the published literature (Ovid Medline and Embase to June 1, 2007) for definitions of CM hemorrhage used in studies of the untreated clinical course of >or=20 participants with CM(s), to inform the development of a consensus statement on the clinical and imaging features of CM hemorrhage at a scientific workshop of the Angioma Alliance.
A systematic review of 1426 publications about CMs in humans, revealed 15 studies meeting our inclusion criteria. Although 14 (93%) studies provided a definition of CM hemorrhage, data were less complete on the confirmatory type(s) of imaging (87%), whether CM hemorrhage should be clinically symptomatic (73%), and whether hemorrhage had to extend outside the CM or not (47%). We define a CM hemorrhage as requiring acute or subacute onset symptoms (any of: headache, epileptic seizure, impaired consciousness, or new/worsened focal neurological deficit referable to the anatomic location of the CM) accompanied by radiological, pathological, surgical, or rarely only cerebrospinal fluid evidence of recent extra- or intralesional hemorrhage. The definition includes neither an increase in CM diameter without other evidence of recent hemorrhage, nor the existence of a hemosiderin halo.
A consistent approach to clinical and brain imaging classification of CM hemorrhage will improve the external validity of future CM research.
The incidence and natural history of the cavernous angioma have remained unclear in part because of the difficulty of diagnosing and following this lesion prior to surgical excision. The introduction of magnetic resonance (MR) imaging has improved the sensitivity and specificity of diagnosing and following this vascular malformation. Seventy-six lesions with an MR appearance typical of a presumed cavernous angioma were discovered in 66 patients among 14,035 consecutive MR images performed at the Cleveland Clinic between 1984 and 1989. Follow-up studies in 86% of the cases over a mean period of 26 months provided 143 lesion-years of clinical survey of this condition. The most frequent presenting features were seizure, focal neurological deficit, and headache. While most lesions exhibited evidence of occult bleeding on MR imaging, there was overt hemorrhage in seven of the 57 symptomatic patients and only one overt hemorrhage occurred during the follow-up interval. The annualized bleeding rate was 0.7%. Analysis of the hemorrhage group revealed a significantly greater risk of overt hemorrhage in females. Pathological confirmation of cavernous angioma was obtained in all 14 surgical cases. This information assists in rational therapeutic planning and prognosis in patients with MR images showing lesions suggestive of cavernous angioma.
The advent of magnetic resonance (MR) imaging has permitted the recognition of many angiographically occult vascular malformations before the development of complications and subsequent surgical removal. This study reviews all patients at one institution who had radiographically identifiable vascular malformations believed to represent cavernous angiomas in order to obtain information on the natural history of this particular lesion. All 8131 craniospinal MR images performed at our medical center from January 1, 1986, to November 30, 1989, were reviewed, and 32 patients were identified with 76 lesions meeting the MR imaging criteria for cavernous angioma. Medical histories, physical examination records, and other data from these patients were then reviewed to determine the frequency of complications. Their mean age at latest follow-up examination (or at surgical removal of the lesion) was 37.6 years (range 16 to 72 years). Sixteen patients (50%) had a history of seizures, seven (22%) had focal neurological deficits, and three (9%) had clinically significant hemorrhage attributable to the cavernous angioma; six patients (19%) were asymptomatic. The estimated risk of hemorrhage for this population is 0.25%/person-year of exposure; the estimated risk of seizure development is 1.51%/person-year. Eight patients underwent surgical procedures, resulting in improved seizure control and/or lessened neurological deficit. Although these lesions are often excised with relative ease and minimal morbidity, the potential risks and benefits of surgery must be weighed carefully before removal of these relatively benign malformations.
A review of 2000 consecutive magnetic resonance imaging (MRI) brain studies identified 18 (0.9%) patients with lesions that satisfied MRI criteria for cavernous haemangiomas. The clinical, computed tomography (CT) and MRI findings in 23 patients with probable cavernous haemangiomas were compared. Thirty-three lesions were identified with multiple lesions in five (22%) patients. In 19 (82%) patients the neurological presentation corresponded to a cavernous haemangioma. The presenting symptoms were: seizures in 11 patients (48%); progressive neurological symptoms and signs in four (17%); and acute symptoms and signs due to haemorrhage in four (17%). T2 weighted images suggested the diagnosis in all cases, with 24 (73%) lesions showing the typical appearance of an area of mixed signal intensity with a rim of low signal intensity. In the absence of acute haemorrhage, CT demonstrated well circumscribed, round or oval hyperdense lesions without significant mass effect and with normal surrounding brain tissue in the majority of cases. Although not diagnostic, these CT features are strongly suggestive of cavernous haemangiomas.
International translation and psychometric testing of generic health outcome measures is increasingly in demand. Following the methodology developed by the International Quality of Life Assessment group (IQOLA) we report the German work with the SF-36 Health Survey. The form was translated using a forward-backward method with accompanying translation quality ratings and pilot tested in terms of translation clarity and applicability. Psychometric evaluation included Thurstone's test of ordinality and equidistance of response choices in 48 subjects as well as testing of reliability, validity, responsiveness and discriminative power of the form in crossectional studies of two samples of healthy persons and longitudinal studies of two samples of pain patients totalling 940 respondents. Quality ratings of translations were favorable, suggesting a high quality of both forward and backward translations. In the pilot study, the form was well understood and easily administered, suggesting high clarity and applicability. Thurstone's test revealed ordinality (in over 90% of the cases) and rough equidistance of response choices also as compared to the American original. On item and scale level, missing data were low and descriptive statistics indicated acceptable distribution characteristics. In all samples studied, discriminative item validity was high (over 90% scaling successes) and Cronbach's alpha reliabilities were above the 0.70 criterion with exception of one scale. Furthermore convergent validity, responsiveness to treatment and discriminative power in distinguishing between healthy and ill respondents was present. The preliminary results suggest that the SF-36 Health Survey in its German form may be a valuable tool in epidemiological and clinical studies. However further work as concerns responsiveness and population based norms is necessary.
This article reviews general information about cavernous malformations, including histology, radiology, epidemiology, and symptomatology. Rates of hemorrhage as reported in the literature are presented. Familial cavernous malformations and their genetic basis are discussed. Finally, the variations in the biological behavior of cavernous malformations in different regions of the central nervous system are discussed and outcomes are assessed.
Prediction of intracerebral hemorrhage (ICH) in patients with cavernous angiomas is not totally elucidated. The aims of our study were to determine the rate of cerebral hemorrhage, its associated factors, and the clinical outcome in patients with cavernous angiomas in a Hispanic population.
We studied 133 patients with cavernous angiomas. The patients were classified into two groups depending on whether they presented an ICH. A comparative analysis of demographics and clinical data, neuroimaging characteristics, and prognosis was carried out in patients with and without hemorrhage. The hemorrhage rate (expressed as the percentage per patient per year) was also estimated.
Seventy-eight patients (59%) had hemorrhage. Non-lobar location of angiomas was associated with hemorrhage [OR 4.82 (CI 95% 2.17-10.73; p=<0.001)]. In contrast, factors associated with a decreased risk of hemorrhage were a family history of epilepsy [OR 0.30 (CI 95% 0.10-0.79; p=0.016)] and lobar location of the angiomas [OR 0.21 (CI 95% 0.09-0.46; p=<0.001)]. The hemorrhagic rate of 1.71% per patient per year was influenced by the location. It was only 1.22% per patient per year in lobar angiomas and 2.33, 2.39, and 2.82% per patient per year for brainstem, cerebellum, and deep hemispheric angiomas, respectively.
The non-lobar location of cavernous angiomas gives a higher risk of hemorrhage in our Mexican mestizo population, without the hemorrhage being related to either age or sex.
Cerebral cavernous malformations (CCM) are vascular malformations that can occur as a sporadic or a familial autosomal dominant disorder. Clinical and cerebral MRI data on large series of patients with a genetic form of the disease are now available. In addition, three CCM genes have been identified: CCM1/KRIT1, CCM2/MGC4607, and CCM3/PDCD10. These recent developments in clinical and molecular genetics have given us useful information about clinical care and genetic counselling and have broadened our understanding of the mechanisms of this disorder.
Pain usually results from activation of nociceptive afferents by actually or potentially tissue-damaging stimuli. Pain may also arise by activity generated within the nervous system without adequate stimulation of its peripheral sensory endings. For this type of pain, the International Association for the Study of Pain introduced the term neuropathic pain, defined as "pain initiated or caused by a primary lesion or dysfunction in the nervous system." While this definition has been useful in distinguishing some characteristics of neuropathic and nociceptive types of pain, it lacks defined boundaries. Since the sensitivity of the nociceptive system is modulated by its adequate activation (e.g., by central sensitization), it has been difficult to distinguish neuropathic dysfunction from physiologic neuroplasticity. We present a more precise definition developed by a group of experts from the neurologic and pain community: pain arising as a direct consequence of a lesion or disease affecting the somatosensory system. This revised definition fits into the nosology of neurologic disorders. The reference to the somatosensory system was derived from a wide range of neuropathic pain conditions ranging from painful neuropathy to central poststroke pain. Because of the lack of a specific diagnostic tool for neuropathic pain, a grading system of definite, probable, and possible neuropathic pain is proposed. The grade possible can only be regarded as a working hypothesis, which does not exclude but does not diagnose neuropathic pain. The grades probable and definite require confirmatory evidence from a neurologic examination. This grading system is proposed for clinical and research purposes.
Health-related quality of life in patients with untreated cavernous malformations of the central nervous system
EUR J NEUROL
Herten A, Chen B, Saban D, et al. Health-related quality of life in
patients with untreated cavernous malformations of the central
nervous system. Eur J Neurol. 2021;28:491-499.
Conceptualization (supporting); data curation (supporting); formal analysis (supporting)
Daniel Mueller: Conceptualization (supporting); data curation (supporting); formal analysis (supporting); investigation (supporting);