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Biomedical subjects

Jaakko Niinimäki

Publications and source records attributed to Jaakko Niinimäki.

12 recordsLinked to original sources

The treatment of disc-herniation-induced sciatica with infliximab: one-year follow-up results of FIRST II, a randomized controlled trial.

STUDY DESIGN: A randomized controlled trial. OBJECTIVES: To evaluate the long-term efficacy of infliximab, a monoclonal antibody against tumor necrosis factor alpha (TNF-alpha), in patients with acute/subacute sciatica secondary to herniated disc. SUMMARY OF BACKGROUND DATA: The results of experimental studies and our open-label trial support the use of infliximab in sciatica. Here we report the 1-year results of a randomized controlled trial (FIRST II, Finnish Infliximab Related STudy) evaluating the efficacy and safety of a single infusion of infliximab for sciatic pain. METHODS: Inclusion criteria were unilateral sciatic pain with a disc herniation concordant with the symptoms and signs of radicular pain. Patients had to be candidates for discectomy. Criteria for discectomy included (in addition to a symptomatic disc herniation on MRI) neural entrapment (straight leg raising [SLR] < or =60 degrees ) with either a short-term (2-4 weeks) severe or long-term (4-12 weeks) moderate leg pain. Forty patients were allocated to a single intravenous infusion of either infliximab 5 mg/kg or placebo. Differences in the clinical examination parameters (straight leg raise [SLR], muscle strength, sensory defects, tendon reflexes), patient-reported symptoms (leg and back pain using a visual analog scale [VAS], Oswestry disability, quality-of-life [RAND-36]), sick leaves, number of discectomies, and adverse effects between the two treatment groups over the 1-year follow-up were compared using Mann-Whitney U test or Student's t test, repeated-measures analysis, or Cox proportional hazards model. Logistic regression was used to assess the predictors of good response. RESULTS: Sixty-seven percent of patients in the infliximab group reported no pain at 52 weeks compared with 63% in the control group (P = 0.72). Similar efficacy was observed between treatment groups for other outcomes. Eight patients in each group required surgery. Three nonserious adverse reactions were encountered in the infliximab group. The response (irrespective of the treatment) was significantly better with shorter symptom duration and less SLR restriction at baseline. Patients in the infliximab group appeared to especially benefit in cases of a L4-L5 (or L3-L4) herniation and if a Modic change was colocalized at the symptomatic level. CONCLUSIONS: Although the long-term results of this randomized trial do not support the use of infliximab compared with placebo for lumbar radicular pain in patients with disc herniation-induced sciatica, further study in a subgroup of patients with L4-L5 or L3-L4 herniations, especially in the presence of Modic changes, appears to be warranted.

Acute Disease↗

The effect of infliximab, a monoclonal antibody against TNF-alpha, on disc herniation resorption: a randomized controlled study.

STUDY DESIGN: Randomized, controlled study. OBJECTIVE: To evaluate the effect of infliximab on herniated nucleus pulposus (HNP) resorption. SUMMARY OF BACKGROUND DATA: Although the effects of tumor necrosis factor alpha (TNF-alpha) on HNP resorption are not fully understood, TNF-alpha appears to be an essential mediator in HNP resorption. METHODS: As part of a substudy of the FIRST II study, magnetic resonance images (MRIs) were obtained from 21 patients who were candidates for discectomy at weeks 0, 2, 12, and 26 after receiving a single infusion of either 5 mg/kg infliximab (11 patients) or placebo (10 patients). The volume (mm3) of HNP, thickness (mm) and extent (%) of rim enhancement, and presence of nerve root edema were assessed. RESULTS: HNP volume decreased significantly from baseline to 6 months in both treatment groups (P < 0.01), with no difference noted between the infliximab and placebo groups. By week 2, rim enhancement thickness increased significantly in the infliximab group compared with the placebo group (P = 0.003). Two patients in each group required back surgery before the 6-month assessment. CONCLUSIONS: Infliximab did not appear to interfere with disc herniation resorption over a 6-month period.

Adult↗

A three-year follow-up of lumbar spine endplate (Modic) changes.

STUDY DESIGN: A longitudinal follow-up of Modic changes on magnetic resonance imaging (MRI). OBJECTIVES: To assess the prevalence and natural course Modic changes over a 3-year follow-up period. SUMMARY OF BACKGROUND DATA: Modic changes are bone marrow and endplate lesions visible on MRI. To the authors' knowledge, no follow-up studies on their natural course have been published. METHODS: The study population consisted of 60 unoperated sciatica patients 23 to 76 years of age. Baseline and 3-year lumbar MR images from L1-L2 through L5-S1 were analyzed independently by 2 radiologists and a consensus reading was performed. RESULTS: At baseline, the prevalence of Modic changes was 23%. Seven discs had mixed Type I/II, and 63 Type II change. Changes typically occurred at L4-L5 and L5-S1, and associated positively with age (P = 0.009). Ten of 70 discs (14%) with Modic changes at baseline displayed another type at 3 years. Furthermore, the nonconverted changes increased significantly in size. The incidence of new Modic changes during the follow-up was 6% (13 of 230). CONCLUSIONS: Modic changes are common MRI findings in patients with degenerative lumbar disc disease. We found evidence that Modic Type II changes may be less stable than previously assumed.

Adult↗

Determinants of spontaneous resorption of intervertebral disc herniations.

STUDY DESIGN: A follow-up of disc herniation (herniated nucleus pulposus [HNP]) resorption on magnetic resonance imaging (MRI). OBJECTIVE: To assess the determinants of resorption of HNP. SUMMARY OF BACKGROUND DATA: Neovascularization in the outermost areas of HNP, presenting as an enhancing rim in gadolinium diethylenetriamine pentaacetic acid MR images, is thought to be a major determinant of spontaneous resorption of HNP. METHODS: Patients with HNP-induced sciatica at baseline were rescanned at 2 months (N = 74) and after 12 months (N = 53). The volume of HNP (mm), thickness (mm) and extent (%) of enhancement, and the degree of HNP migration (Komori classification) were analyzed. Repeated measures analysis of covariance was used in statistical analysis. RESULTS: Significant resorption of HNP occurred from baseline to 2 months, although the resorption rate was more pronounced over the whole 1-year follow-up. Higher baseline scores of rim enhancement thickness, higher degree of HNP displacement in the Komori classification, and age category 41-50 years were associated with a higher resorption rate. Thickness of rim enhancement was a stronger determinant of spontaneous resorption than extent of rim enhancement. Clinical symptom alleviation occurs concordantly with a faster resorption rate. CONCLUSIONS: MRI is a useful prognostic tool for identifying patients with HNP-induced sciatica with a benign natural course.

Adult↗

The treatment of disc herniation-induced sciatica with infliximab: results of a randomized, controlled, 3-month follow-up study.

STUDY DESIGN: A randomized controlled trial. OBJECTIVES: To evaluate the efficacy of infliximab, a monoclonal antibody against tumor necrosis factor (TNF)-alpha in a randomized controlled setting. SUMMARY OF BACKGROUND DATA: Recently, we obtained encouraging results in an open-label study of infliximab in patients with disc herniation-induced sciatica. Furthermore, the results of experimental studies support the use of infliximab in sciatica. Therefore, we initiated a randomized, controlled trial (FIRST II, Finnish Infliximab Related STudy) to confirm the efficacy of a single infusion of infliximab for sciatic pain. METHODS: Inclusion criteria were unilateral moderate to severe sciatic pain with an MRI-confirmed disc herniation concordant with the symptoms and signs of radicular pain. Patients had to be candidates for discectomy, as evaluated by an independent orthopedic surgeon. Forty patients were allocated to a single intravenous infusion of either infliximab 5 mg/kg or placebo. Assessments at baseline and various time points included clinical examination with measurement of straight leg raising restriction; questionnaires related to subjective symptoms (leg and back pain by 100-mm visual analog scale, Oswestry disability); sick leaves; number of discectomies; and adverse effects possibly related to treatment. The primary endpoint was a reduction in leg pain from baseline to 12 weeks, which was analyzed using a Mann-Whitney U test and repeated-measures analysis. RESULTS: A significant reduction in leg pain was observed in both groups, with no significant difference between treatment regimens. Similar efficacy was observed between treatment groups for secondary endpoints. Seven patients in each group required surgery. No adverse effects related to treatment were encountered. CONCLUSIONS: The results of this randomized trial do not support the use of infliximab for lumbar radicular pain in patients with disc herniation-induced sciatica.

Adult↗

BOLD signal increase preceeds EEG spike activity--a dynamic penicillin induced focal epilepsy in deep anesthesia.

In 40-60% of cases with interictal activity in EEG, fMRI cannot locate any focus or foci with simultaneous EEG/fMRI. In experimental focal epilepsy, a priori knowledge exists of the location of the epileptogenic area. This study aimed to develop and to test an experimental focal epilepsy model, which includes dynamic induction of epileptic activity, simultaneous EEG/fMRI, and deep anesthesia. Reported results are from seven pigs (23 +/- 2 kg) studied under isoflurane anesthesia (1.2-1.6 MAC, burst-suppression EEG) and muscle relaxant. Hypo- and hypercapnia were tested in one pig. Penicillin (6000 IU) was injected via a plastic catheter (inserted into the somatosensory cortex) during fMRI (GRE-EPI, TE = 40 ms, 300 ms/two slices, acquisition delay 1700 ms) in 1.5 T (N = 6). Epileptic spikes between acquisition artifacts were reviewed and EEG total power calculated. Cross-correlation between voxel time series and three model functions resembling induced spike activity were tested. Activation map averages were calculated. Development of penicillin induced focal epileptic activity was associated with linear increase and saturation up to approximately 10-20%, in BOLD activation map average. Its initial linear increase reached 2.5-10% at the appearance of the first distinguished spike in ipsilateral EEG in all six animals. Correlated voxels were located mainly in the vicinity of the penicillin injection site and midline, but few in the thalamus. In conclusion, development of focal epileptic activity can be detected as a BOLD signal change, even preceding the spike activity in scalp EEG. This experimental model contains potential for development and testing different localization methods and revealing the characteristic time sequence of epileptic activity with fMRI during deep anesthesia.

Anesthesia↗

Interventional and intraoperative MRI at low field scanner--a review.

Magnetic resonance imaging (MRI) is a cutting edge imaging modality in detecting diseases and pathologic tissue. The superior soft tissue contrast in MRI allows better definition of the pathology. MRI is increasingly used for guiding, monitoring and controlling percutaneous procedures and surgery. The rapid development of interventional techniques in radiology has led to integration of imaging with computers, new therapy devices and operating room like conditions. This has projected as faster and more accurate imaging and hence more demanding procedures have been applied to the repertoire of the interventional radiologist. In combining features of various other imaging modalities and adding some more into them, interventional MRI (IMRI) has potential to take further the interventional radiology techniques, minimally invasive therapies and surgery. The term "Interventional MRI" consists in short all those procedures, which are performed under MRI guidance. These procedures can be either percutaneous or open surgical of nature. One of the limiting factors in implementing MRI as guidance modality for interventional procedures has been the fact, that most widely used magnet design, a cylindrical magnet, is not ideal for guiding procedures as it does not allow direct access to the patient. Open, low field scanners usually operating around 0.2 T, offer this feature. Clumsy hardware, bad patient access, slow image update frequency and strong magnetic fields have been other limiting factors for interventional MRI. However, the advantages of MRI as an imaging modality have been so obvious that considerable development has taken place in the 20-year history of MRI. The image quality has become better, ever faster software, new innovative sequences, better MRI hardware and increased computing power have accelerated imaging speed and image quality to a totally new level. Perhaps the most important feature in the recent development has been the introduction of open configuration low field MRI devices in the early 1990s; this enabled direct patient access and utilization of the MRI as an interventional device. This article reviews the current status of interventional and intraoperative MRI with special emphasis in low field surrounding.

Humans↗

Efficacy of infliximab for disc herniation-induced sciatica: one-year follow-up.

STUDY DESIGN: An open-label trial. OBJECTIVES: To test the long-term efficacy of infliximab, a monoclonal antibody against tumor necrosis factor-alpha (TNF-alpha), in disc herniation-induced sciatica. SUMMARY OF BACKGROUND DATA: Our recent trial indicated that a single infusion of 3 mg/weight-kg of infliximab produced a rapid curative effect in disc herniation-induced sciatica. Here, we describe the 1-year effect of a 3 mg/kg of infliximab in these 10 patients and our experience with a lower dose of 1 mg/kg of infliximab for the same indication in 2 additional patients. METHODS: Patients with severe sciatica were treated with a single infusion of infliximab, 3 mg/weight-kg in 10 patients and 1 mg/kg in 2 patients, intravenously over 2 hours. The outcomes (leg and back pain on a 100-mm visual scale, Oswestry disability, clinical signs) were assessed at 1 week, 2 weeks, 1 month, 3 months, 6 months, and 1 year after the infusion. The outcomes with 3 mg/kg of infliximab were compared to 62 patients who received periradicular saline for sciatica in a previous trial. The resorption rate of disc herniations from baseline to 1 year was compared between infliximab and control groups. RESULTS: The response to 1 mg/kg of infliximab for leg pain was good only in 1 of the 2 patients treated, whereas the response to 3 mg/kg of infliximab for leg pain was sustained in most patients over the 1-year follow-up. The 1-year response significantly favored 3 mg/kg of infliximab over periradicular saline in leg pain (P = 0.005) and disability (P = 0.003). Neurologic abnormalities normalized more comprehensively in the infliximab group (P = 0.001). Reduction in disc herniation volume did not differ between the infliximab-treated patients and controls. CONCLUSIONS: The results showed that the beneficial effect of a single infusion of 3 mg/kg of infliximab for herniation-induced sciatica is sustained in most patients over a 1-year follow-up period. Furthermore, infliximab does not seem to interfere with the spontaneous resorption of disc herniations.

Antibodies, Monoclonal↗

Three-year follow-up of lumbar artery occlusion with magnetic resonance angiography in patients with sciatica: associations between occlusion and patient-reported symptoms.

STUDY DESIGN: Comparison of occlusion of lumbar arteries in magnetic resonance angiography (MRA) with patient-reported sciatica symptoms during a 3-year follow-up. OBJECTIVES: To evaluate whether occlusion of lumbar arteries is associated with subjective pain symptoms and physical ability among sciatica patients. SUMMARY OF BACKGROUND DATA: Cadaveric studies indicate that atherosclerotic manifestations of the abdominal aorta are associated with low back pain (LBP). Impaired blood flow may disturb diffusion of nutrients into the disc, causing degeneration and possibly back pain. METHODS: Two-dimensional time-of-flight MRA was used to evaluate lumbar arteries at baseline and 3 years. The arteries on both sides (L1-L4) were evaluated visually and scored as normal, narrowed, or occluded. Incidence of new stenosis was estimated. The associations of stenosis with self-reported previous medical consultations, pain duration through the first year, and number of pain episodes through the last 2 years of follow-up were calculated. Additionally, leg and back pain (10-cm VAS), disability (Oswestry), and self-reported physical ability (self-efficacy) were inquired at 1, 2, and 3 years. In the statistical analysis, bivariate correlation, and the chi or Fisher's test were used. RESULTS: MRA was obtained at baseline for 147 patients and at 3 years for 134 patients. Baseline stenosis associated with intensity of back pain at 1 year, leg pain at 2 years, and self-efficacy at every follow-up assessment, but not with disability, previous LBP history, or future pain episodes. The associations of stenosis at 3 years were similar but weaker. Newly formed stenosis was associated with the preceding year's medical consultations due to LBP and prolonged LBP during the first follow-up year. CONCLUSIONS: Arterial stenosis is associated strongly and consistently with patient-estimated physical ability,but only slightly with subjective pain symptoms. Interestingly, new stenosis is preceded by pain symptoms. The evaluation of lumbar blood flow may thus be useful in clinical practice.

Adult↗

Tumor necrosis factor-alpha monoclonal antibody, infliximab, used to manage severe sciatica.

STUDY DESIGN: An open-label study was conducted. OBJECTIVE: To evaluate the efficacy and safety of infliximab, a monoclonal chimeric antibody, against tumor necrosis factor-alpha (TNFalpha) for the treatment of severe sciatica. SUMMARY OF BACKGROUND DATA: Evidence from animal studies indicates that TNFalpha plays a role in the pathophysiology of sciatica. Anti-TNFalpha therapy has not been previously evaluated in sciatic patients. METHODS: In this study, 10 patients with disc herniation-induced severe sciatica received infliximab (Remicade 3 mg/kg) intravenously over 2 hours. The outcome was assessed at 1 hour, 1 week, 2 weeks, 1 month, and 3 months after the infusion and compared to historical control subjects consisting of 62 patients who received saline in a trial of periradicular infiltration for sciatica. Leg pain was the primary outcome, with more than a 75% decrease from the baseline score constituting a painless state. Fisher's exact test and repeated measures analysis of variance were used for statistical analysis. RESULTS: At 1 hour after the infusion, leg pain had decreased by 50%. At 2 weeks, 60% of the patients in the infliximab group were painless, as compared with 16% of the control patients (P = 0.006). The difference was sustained at 3 months (90% vs 46%; P = 0.014). Infliximab was superior over the whole follow-up period in terms of leg pain (P = 0.003) and back-related disability (P = 0.004). At 1 month, every patient in the infliximab group had returned to work, whereas 38% of the control subjects still were on sick leave (P = 0.02). None of the patients treated with infliximab underwent surgery during the follow-up period. No immediate or delayed adverse drug reactions and no adverse effects related to medication were observed. CONCLUSIONS: Anti-TNFalpha therapy is a promising treatment option for sciatica. There is an urgent need for a randomized controlled trial to evaluate whether thesepromising early results can be confirmed.

Adult↗

A portable diagnostic workstation based on a Webpad: implementation and evaluation.

A wireless hand-held Webpad device was used to review a sample set of cranial computerized tomography (CT) studies to assess its diagnostic capabilities and its feasibility as a portable diagnostic workstation for radiology. The data-set consisted of 30 head CT studies of emergency cases. Two neuroradiologists and a senior radiologist participated in the evaluation of the portable workstation. They used a Web-based viewer that we developed, which provided all the major functionalities required for radiological image review. The reported radiological findings and diagnoses were compared with a gold standard, comprising a set of diagnoses previously formulated by a consensus panel of radiologists who had reviewed the original studies. The diagnoses made using the Webpad were correct (no major discrepancies) in 82 out of 90 interpretations (91%), which is comparable to the accuracy reported in image review with a conventional radiological workstation. The average total working time per diagnosis was 5 min 25 s (range 2-12 min). The simplicity of use of the system and its low cost make it suitable for distributing radiological studies within hospital facilities.

Adolescent↗