Can repetitive transcranial magnetic stimulation increase muscle strength in functional neurological paresis? A proof-of-principle study.

BACKGROUND AND PURPOSE: Therapeutic options are limited in functional neurological paresis disorder. Earlier intervention studies did not control for a placebo effect, hampering assessment of effectivity. A proof-of-principle investigation was conducted into the therapeutic potential of repetitive transcranial magnetic stimulation (rTMS), using a single-blind two-period placebo-controlled cross-over design. METHODS: Eleven patients received active 15 Hz rTMS over the contralateral motor cortex (hand area), in two periods of 5 days, for 30 min once a day at 80% of resting motor threshold, with a train length of 2 s and an intertrain interval of 4 s. Eight of these eleven patients were also included in the placebo treatment condition. Primary outcome measure was change in muscle strength as measured by dynamometry after treatment. Secondary outcome measure was the subjective change in muscle strength after treatment. RESULTS: In patients who received both treatments, active rTMS induced a significantly larger median increase in objectively measured muscle strength (24%) compared to placebo rTMS (6%; P < 0.04). Subjective ratings showed no difference due to treatment, i.e. patients did not perceive these objectively measured motor improvements (P = 0.40). CONCLUSIONS: Our findings suggest that rTMS by itself can potentially improve muscle weakness in functional neurological paresis disorder. Whereas patients' muscle strength increased as measured with dynamometry, patients did not report increased functioning of the affected hand, subjectively. The results may indicate that decreased muscle strength is not the core symptom and that rTMS should be added to behavioral approaches in functional neurological paresis.

tPA treatment for acute ischaemic stroke in patients with leukoaraiosis.

BACKGROUND AND PURPOSE: Whether leukoaraiosis on baseline CT is associated with an increased risk of symptomatic intracerebral haemorrhage (sICH) or poor outcome following tissue plasminogen activator (tPA) treatment for acute ischaemic stroke is still a matter of debate. OBJECTIVE: To investigate the relationship between the presence and severity of leukoaraiosis on baseline CT and the risk of sICH and functional outcome after tPA treatment for acute ischaemic stroke. METHODS: A single-center observational cohort study with a retrospective analysis on consecutive patients with ischaemic stroke treated with tPA in the period 2002-2008. Outcome measures were the occurrence of sICH and functional outcome at 3 months. RESULTS: Of the 400 patients, 24% had leukoaraiosis on their baseline CT. Eleven patients (11%) with leukoaraiosis versus thirteen (4%) patients without leukoaraiosis had a sICH [odds ratio (OR) 2.85 95%-CI 1.23-6.60, P = 0.02]. Multivariate analysis showed a non-significant trend towards an association of leukoaraiosis and sICH (OR 1.9, 95%-CI 0.78-4.68, P = 0.16). Leukoaraiosis was independently associated with poor functional outcome (OR 2.39, 95%-CI 1.21-4.72, P = 0.01). No difference was observed in the outcome measures amongst patients with moderate or severe leukoaraiosis. CONCLUSION: Our study demonstrates that patients treated with tPA and leukoaraiosis on their baseline CT are at greater risk of sICH and have a worse functional outcome compared to patients without leukoaraiosis. It is important to note that these results should not lead to exclusion of patients with leukoaraiosis for tPA treatment.

Development and validation of a predictive outcome score of cerebral venous thrombosis.

BACKGROUND AND PURPOSE: Cerebral venous thrombosis (CVT) is a rare disease with a variable outcome. The aim of this study was to develop and validate a predictive outcome score for CVT patients. METHODS: The score was based on the 8 predictive variables of poor outcome (modified Rankin Scale score>2) from the International Study on Cerebral Vein and Dural Sinus Thrombosis: age >37, male, mental status disorder, coma, intracranial hemorrhage, deep CVT, CNS infection, and malignancy. To assign a weighted index (WI), the natural logarithm of the hazard ratio of each variable was calculated, multiplied by 10 and rounded to the nearest integer. The individual score of each patient was the sum of the WI. The validation sample consisted of a retrospective single center cohort of 90 CVT patients. RESULTS: Sixteen patients (18%) had a poor outcome. The predictive score had an area under the receiver operating characteristic curve of 0.81 (95% CI 0.71-0.90). The cut-off score with the maximum sum of sensitivity and specificity was a score> or =14 with sensitivity of 88% (81%-95%) and specificity of 70% (61%-79%). The predictive value of a score<14 for good outcome was 96% (92%-100%), whereas the predictive value of a score> or =14 for poor outcome was 39% (29%-49%). CONCLUSIONS: This relatively simple predictive outcome score may be useful in CVT patients. A cut-off score of 14 reliably predicts good outcome, but is less accurate in predicting poor outcome.

Does smoking influence outcome after intravenous thrombolysis for acute ischaemic stroke?

BACKGROUND AND PURPOSE: It remains uncertain whether current smoking influences outcome in patients with acute ischaemic stroke. OBJECTIVES: To evaluate the effect of current smoking in routinely tissue plasminogen activator (tPA)-treated stroke patients on the 3-month functional outcome and the occurrence of symptomatic intracerebral hemorrhage (ICH). METHODS: We analyzed data from a single stroke care unit registry of 345 consecutive patients with ischaemic stroke, treated with tPA. Logistic regression models were used to assess if smoking was independently associated with 3-months good outcome defined as a modified Rankin Scale score of < or =2, and the occurrence of symptomatic ICH. RESULTS: In the multivariable models, smoking was not associated with a good outcome or a decreased risk of symptomatic ICH. CONCLUSION: Current smoking did not affect functional outcome at 3 months or the risk of symptomatic ICH in patients routinely treated with tPA for ischaemic stroke.

Utility of the stroke-thrombolytic predictive instrument.

OBJECTIVE: The goal of this study was to evaluate the utility of the stroke thrombolytic predictive instrument (s-TPI) in predicting clinical outcome in patients with acute ischaemic stroke treated with intravenous tissue plasminogen activator (t-PA). METHODS: The study assessed the external validity of the s-TPI in 301 consecutive stroke patients treated with intravenous t-PA. Clinical outcome was measured with the modified Rankin scale (mRs) at 3 months. The study used the s-TPI to calculate probabilities of a good outcome (mRs 0-1) and a poor outcome (mRs 5-6). We compared these probabilities with the observed outcome using receiver-operator characteristics (ROC) curves and calibration curves. Subgroup analyses for different onset-to-treatment time windows were performed. RESULTS: According to the s-TPI, the mean predicted probability of a good and a poor outcome in the validation cohort were 0.45 and 0.17. The area under the ROC curves were 0.80 (4.5-hour time window), 0.82 (3-hour time window) and 0.77 (3-4.5 hours time window) for predicting good outcome, and 0.78 (4.5 hours), 0.80 (3 hours) and 0.74 (3-4.5 hours) for predicting poor outcome. Calibration curves revealed a slight overestimation of probabilities of a good outcome and underestimation of probabilities of a poor outcome. CONCLUSIONS: The s-TPI appears to be reasonably valid for predicting outcome after t-PA treatment in daily practice, although a slight overestimation of a good and underestimation of a poor outcome was observed.

Lipid profile, statin use, and outcome after intravenous thrombolysis for acute ischaemic stroke.

BACKGROUND: Low cholesterol levels have been associated with an increased risk of haemorrhagic stroke. This study investigated whether lipid levels or prior statin use influence outcome in patients with acute ischaemic stroke treated with IV thrombolysis. METHODS: The relation between admission lipid levels or statin use and both the development of symptomatic intracerebral haemorrhage (sICH) and 3-months functional outcome was assessed in a prospective hospital-based stroke registry comprising 252 patients treated with IV tissue plasminogen activator (tPA). The fasting status of the patients was unknown. Favourable outcome at 3 months was defined as a modified Rankin scale score

Measuring disability in stroke: relationship between the modified Rankin scale and the Barthel index.

BACKGROUND AND PURPOSE: The effectiveness of therapeutic interventions in acute stroke trials is traditionally measured with the modified Rankin scale (mRs) and the Barthel index (BI). The mRs is a global disability scale divided into six steps from total independence to total dependence. The BI assesses ten basal activities of daily living, of which eight assess level of dependence (bathing, grooming, using stairs, dressing, feeding, toilet use, transfers and walking). The aim of this study was to investigate the relationship between the mRs and the total scores and item-scores of the BI. METHODS: During a period of 3 months mRs and BI scores were collected from two multicentre randomised, placebo-controlled trials with lubeluzole (515 and 519 patients). In each patient we compared the mRs grades with the total BI score and the scores on the ten subitems. RESULTS: For both trials there was extensive overlap of BI scores between mRs grades and a wide range in BI scores among patients with mRs grades 3 and 4. We also found discrepancies between the BI item-scores and mRs grades. About 40% of patients with mRs grades 1 (able to carry out all usual activities) and 2 (able to look after own affairs without assistance) were not independent on at least one activity of the BI. In both studies, about 30% of the patients needed help or supervision for walking, although they were classified as mRs 3 (requiring some help but able to walk without assistance). CONCLUSIONS: Investigators in stroke trials use the mRs as a subjective global disability scale, and they do not strictly take into account limitations in performing specific basal activities of daily living, as assessed by the BI, to assign mRs grades.

Safety of routine IV thrombolysis between 3 and 4.5 h after ischemic stroke.

BACKGROUND: The administration of tissue plasminogen activator (t-PA) has been proven effective for ischemic stroke within 3 h after onset. A pooled-analysis of six trials showed that intravenous t-PA still improves outcome when given between 3 to 4.5 h after stroke onset. On the basis of this pooled analysis, t-PA was also routinely offered to our patients between 3-4.5 h. We report the safety and clinical features of this group together with the features of the group given t-PA within 3 h. METHODS: Prospectively patient characteristics, stroke severity, stroke subtype, incidence of symptomatic intracerebral hemorrhage (SICH), in-hospital mortality, and 3-months modified Rankin Scale scores (mRS) were registered. Data was analyzed separately for patients treated within 3 h (early group) and those treated between 3-4.5 h (late group). RESULTS: Among 176 patients who underwent intravenous thrombolysis, 101 were treated in the early group and 75 in the late group. Six (5.9%; 95% CI 2.8%-12.3%) patients in the early group and 4 (5.3%; 95% CI 2.2%-12.9%) in the late group developed SICH (p=1.0). In the early group 13 (12.9%; 95% CI 7.7%-20.8%) patients died within 7 days after admission, compared to 5 (6.7%; 95% CI 3.0%-14.7%) in the late group (p=0.179). In the early group 44 (43.6%; 95% CI 43.3%-53.3%) were independent (mRS< or =2) at three months, compared to 36 (48.0%; 95% CI 37.0%-59.1%) in the late group (p=0.559). CONCLUSION: Our data show no trend of decreased safety of thrombolysis beyond 3 h. Due to a small sample size a harmful effect cannot be excluded but seems unlikely.

Pitfalls in the diagnosis of reversible cerebral vasoconstriction syndrome and primary angiitis of the central nervous system.

A case of a 51-year-old woman with reversible cerebral vasoconstriction syndrome (RCVS) without an associative cause is reported. Initially the diagnosis primary angiitis of the central nervous system (PACNS) was considered. Both diagnosis are rare and can mimic each other. Distinction between both can be difficult, but is necessary because of different treatment options. Clinical features and diagnostic assessments to distinguish RCVS from PACNS and the potential pitfalls are discussed.

Study protocol for a randomised controlled multicentre study: the Foraminotomy ACDF Cost-Effectiveness Trial (FACET) in patients with cervical radiculopathy.

INTRODUCTION: Cervical radiculopathy due to discogenic or spondylotic stenosis of the neuroforamen can be surgically treated by an anterior discectomy with fusion (ACDF) or a posterior foraminotomy (FOR). Most surgeons prefer ACDF, although there are indications that FOR is as effective as ACDF, has a lower complication rate and is less expensive. A head-to-head comparison of the 2 surgical techniques in a randomised controlled trial has not yet been performed. The study objectives of the Foraminotomy ACDF Cost-Effectiveness Trial (FACET) study are to compare clinical outcomes, complication rates and cost-effectiveness of FOR to ACDF. METHODS AND ANALYSIS: The FACET study is a prospective randomised controlled trial conducted in 7 medical centres in the Netherlands. The follow-up period is 2 years. The main inclusion criterion is a radiculopathy of the C4, C5, C6 or C7 nerve root, due to a single-level isolated cervical foraminal stenosis caused by a soft disc and/or osteophytic component, requiring operative decompression. A sample size of 308 patients is required to test the hypothesis of clinical non-inferiority of FOR versus ACDF. Primary outcomes are: 'operative success', the measured decrease in radiculopathy assessed by the visual analogue scale and 'patient success', assessed by the modified Odom's criteria. Secondary outcomes are: Work Ability Index (single-item WAI), quality of life (EuroQol 5 Dimensions 5 level Survey, EQ-5D-5L), Neck Disability Index (NDI) and complications. An economic evaluation will assess cost-effectiveness. In addition, a budget impact analysis will be performed. ETHICS AND DISSEMINATION: Ethical approval was obtained from the Institutional Ethics Committee of the University Medical Center Groningen. Results of this study will be disseminated through national and international papers. The participants and relevant patient support groups will be informed about the results of the study. TRIAL REGISTRATION NUMBER: NTR5536, pre-results.

Diagnostic value of history and physical examination in patients suspected of sciatica due to disc herniation: a systematic review.

We conducted a systematic review of the literature from 1965-1994 to assess the value of history and physical examination in the diagnosis of sciatica due to disc herniation; we also included population characteristics and features of the study design affecting diagnostic value. Studies on the diagnostic value of history and physical examination in the diagnosis of sciatica due to disc herniation are subject to important biases, and information on numerous signs and symptoms is scarce or absent. Our search revealed 37 studies meeting the selection criteria; these were systematically and independently read by three readers to determine diagnostic test properties using a standard scoring list to determine the methodological quality of the diagnostic information. A meta-analysis was performed when study results allowed statistical pooling. Few studies investigated the value of the history. Pain distribution seemed to be the only useful history item. Of the physical examination signs the straight leg raising test was the only sign consistently reported to be sensitive for sciatica due to disc herniation. However, the sensitivity values varied greatly, the pooled sensitivity and specificity values being 0.85 and 0.52, respectively. The crossed straight leg raising test was the only sign shown to be specific; the pooled sensitivity and specificity values were 0.30 and 0.84, respectively. There was considerable disagreement on the specificity of the other neurological signs (paresis, sensory loss, reflex loss). Several types of bias and other methodological drawbacks were encountered in the studies limiting the validity of the study results. As a result of these drawbacks it is probable that test sensitivity was overestimated and test specificity underestimated.

Pathoanatomy of clinical findings in patients with sciatica: a magnetic resonance imaging study.

OBJECT: Anatomical details of nerve root compression may explain the production of the signs and symptoms of sciatica. The authors of anatomical studies have offered many theories without clearly demonstrating the clinical relevance of the observations. Clinicoanatomical series are scarce and are affected to a great extent by selection bias. METHODS: The authors created a schematic drawing of the lumbar anatomy based on both the literature and in vitro anatomical observations. A diagnosis was then made with the aid of detailed and standardized clinical and magnetic resonance (MR) imaging studies in primary-care patients who presented with pain that radiated into the leg. Clinical and MR imaging findings were correlated. Finally, the anatomical drawing was compared with the clinical data. The higher the vertebral level of symptomatic disc herniations, the more likely the compression will be more laterally situated. Classic symptoms of sciatica (typically, dermatomal pain; increase in pain when coughing, sneezing, or straining; and testing positive for pain during straight leg raising) were most likely to occur with compression of the nerve root in the axilla and with mediolateral disc herniations. CONCLUSIONS: The L-3, L-4, L-5, and S-1 nerve roots each tend to be compressed at different sites along the rostrocaudal course of the nerve root. Disc herniations become symptomatic at different sites for each disc level. The schematic drawing produced a priori could well be used to explain these findings. Expectations of particular clinical findings can be predicted by specific pathoanatomical findings.

Consistency of history taking and physical examination in patients with suspected lumbar nerve root involvement.

STUDY DESIGN: A cross-sectional study of interobserver variability in primary care patients. OBJECTIVE: To investigate the consistency of signs and symptoms of nerve root compression in primary care patients with pain irradiating pain into the leg (sciatica). SUMMARY OF BACKGROUND DATA: The literature does not report on all the clinical tests for nerve root compression. In previous studies, most patients had low back pain with no irradiation. Often, little information on examination technique, proportion of positive test results, or clinical patient characteristics was provided. METHODS: A random selection of 91 patients was investigated by a neurologist-resident couple. Agreement percentages, proportions of positive test results, and kappas were calculated. RESULTS: The kappa of the overall conclusion after the history taking was 0.40, increasing to 0.66 after physical examination. Kappas were good for decreased muscle strength and sensory loss (0.57-0.82), intermediate for reflex changes (0.42-0.53), and poor for the examination of the lumbar spine (0.16-0.33). The straight leg raising, crossed straight leg raising, Bragard's sign, and Naffziger's sign were the most consistent nerve root tension signs (> 0.66). CONCLUSIONS: Two clinicians disagreed on the presence of nerve root involvement in one of four patients after history taking, and in one of five patients after physical examination. For a more consistent overall diagnosis, the physician probably should put more emphasis on the history of pain on coughing-straining-sneezing, a feeling of coldness in the legs, and urinary incontinence. The investigation of paresis, sensory loss, reflex changes, straight leg raising, and Bragard's sign provide the most consistent results.

[Lumbosacral radicular syndrome: good chance for recovery even without MRI diagnosis and treatment]. / Het lumbosacrale radiculaire syndroom: ook zonder MRI-diagnostiek en behandeling grote kans op herstel.

Two men aged 32 and 39 years had had sciatica for one week and 12 weeks, respectively. In both MRI revealed a prolapsed disc. The first patient recovered spontaneously after 9 weeks, the other recovered after discectomy. After a clinical diagnosis of sciatica, the question arises when additional diagnostic procedures are called for. This question is closely related to the treatment of sciatica. Spontaneous recovery occurs in many patients with sciatica whereas non-invasive therapies including bed rest show a relative lack of effectiveness. While surgical intervention is an effective therapy, the high rate of surgical procedures for disc herniation in the Netherlands compared with most other industrialised countries calls for a critical appraisal of indications for surgery.

Reproducibility and variability of dynamic cerebral autoregulation during passive cyclic leg raising.

Dynamic cerebral autoregulation (dCA) estimates require mean arterial blood pressure (MABP) fluctuations of sufficient amplitude. Current methods to induce fluctuations are not easily implemented or require patient cooperation. In search of an alternative method, we evaluated if MABP fluctuations could be increased by passive cyclic leg raising (LR) and tested if reproducibility and variability of dCA parameters could be improved. Middle cerebral artery cerebral blood flow velocity (CBFV), MABP and end tidal CO2 (PetCO2) were obtained at rest and during LR at 0.1 Hz in 16 healthy subjects. The MABP-CBFV phase difference and gain were determined at 0.1 Hz and in the low frequency (LF) range (0.06-0.14 Hz). In addition the autoregulation index (ARI) was calculated. The LR maneuver increased the power of MABP fluctuations at 0.1 Hz and across the LF range. Despite a clear correlation between both phase and gain reproducibility and MABP variability in the rest condition, only the reproducibility of gain increased significantly with the maneuver. During the maneuver patients were breathing faster and more irregularly, accompanied by increased PetCO2 fluctuations and increased coherence between PetCO2 and CBFV. Multiple regression analysis showed that these concomitant changes were negatively correlated with the MABP-CBFV phase difference at 0.1 Hz Variability was not reduced by LR for any of the dCA parameters. The clinical utility of cyclic passive leg raising is limited because of the concomitant changes in PetCO2. This limits reproducibility of the most important dCA parameters. Future research on reproducibility and variability of dCA parameters should incorporate PetCO2 variability or find methods to keep PetCO2 levels constant.

Hyperdense middle cerebral artery sign and outcome after intravenous thrombolysis for acute ischemic stroke.

BACKGROUND: The presence of a hyperdense middle cerebral artery sign (HMCAS) on baseline brain CT is associated with poor clinical outcome in stroke patients treated with intravenous recombinant tissue plasminogen activator (tPA). It remains uncertain whether the presence of HMCAS is associated with acute neurological deterioration after tPA treatment. OBJECTIVE: To evaluate the effect of HMCAS in routinely intravenous tPA-treated patients with anterior circulation stroke on acute neurological deterioration, the 3-month functional outcome and the occurrence of symptomatic ICH. METHODS: We analyzed data from a single stroke unit registry of 384 consecutive patients with anterior circulation infarction, treated with intravenous tPA. Logistic regression models were used to assess if HMCAS was independently associated with predefined outcome definitions. RESULTS: We found a HMCAS in 104 patients (27%). The HMCAS was related to the risk of early neurological deterioration (p=0.04) and poor functional outcome (p<0.001) on univariate analysis. The incidence of symptomatic ICH was not significantly different between patients with and without HMCAS (7% versus 6%, p=0.81). In the multivariable analysis, the presence of HMCAS was significantly associated with a poor outcome (p=0.004). CONCLUSIONS: The HMCAS is associated with early neurological deterioration and poor functional outcome, but not with symptomatic ICH.