Paul J. A. M. Brouwers

A cervical anterior spinal artery syndrome after diagnostic blockade of the right C6-nerve root.

A 48-year-old man suffered from intractable neck pain irradiating to his right arm. Magnetic resonance imaging (MRI) of the cervical spine was unremarkable. A right-sided diagnostic C6-nerve root blockade was performed. Immediately following this seemingly uneventful procedure he developed a MRI-proven fatal cervical spinal cord infarction. We describe the blood supply of the cervical spinal cord and suggest that this infarction resulted from an impaired perfusion of the major feeding anterior radicular artery of the spinal cord, after local injection of iotrolan, bupivacaine, and triamcinolon-hexacetonide around the C6-nerve root on the right side.

Disturbances of calcium homeostasis in ischaemic stroke - Therapeutic implications

In Western societies, stroke represents the third largest cause of death and the main cause of disability. With an expected increase of stroke incidence in the near future, much research is being devoted to the development of an effective treatment. At present, however, no such treatment is available, although thrombolysis may be beneficial in a small percentage of patients with ischaemic stroke.The use of neuroprotective agents that protect neurons against the effects of ischaemia is appealing. Some neuroprotective drugs are believed to exert their effects by influencing calcium homeostasis in potentially viable brain cells in the ischaemic penumbra, the area surrounding the core of the infarct. A massive calcium ion (Ca++) influx into these cells plays an important role in the final common pathway of cell death. Ca++ can enter cells by voltage-sensitive calcium channels or by agonist-operated calcium channels. Calcium antagonists acting on several subtypes of these channels are capable of decreasing Ca++ influx into ischaemic brain cells.In animal studies, many calcium antagonists reduce infarct size or increase cerebral blood flow. However, clinical trials with calcium antagonists have been disappointing and at present an effective neuroprotective agent has not been identified. Recently, concerns have arisen about the adverse effects of calcium antagonists acting on voltage-sensitive calcium channels.

Metformin and sitAgliptin in patients with impAired glucose tolerance and a recent TIA or minor ischemic Stroke (MAAS): study protocol for a randomized controlled trial

BackgroundImpaired glucose tolerance is present in one third of patients with a TIA or ischemic stroke and is associated with a two-fold risk of recurrent stroke. Metformin improves glucose tolerance, but often leads to side effects.The aim of this study is to explore the feasibility, safety, and effects on glucose metabolism of metformin and sitagliptin in patients with TIA or minor ischemic stroke and impaired glucose tolerance. We will also assess whether a slow increase in metformin dose and better support and information on this treatment will reduce the incidence of side effects in these patients.Methods/DesignThe Metformin and sitAgliptin in patients with impAired glucose tolerance and a recent TIA or minor ischemic Stroke trial (MAAS trial) is a phase II, multicenter, randomized, controlled, open-label trial with blinded outcome assessment. Non-diabetic patients (n = 100) with a recent (<6 months) TIA, amaurosis fugax or minor ischemic stroke (modified Rankin scale ≤ 3) and impaired glucose tolerance, defined as 2-hour post-load glucose levels between 7.8 and 11.0 mmol/L after repeated standard oral glucose tolerance test, will be included. Patients with renal or liver impairment, heart failure, chronic hypoxic lung disease stage III–IV, history of lactate acidosis or diabetic ketoacidosis, pregnancy or breastfeeding, pancreatitis and use of digoxin will be excluded. The patients will be randomly assigned in a 1:1:2 ratio to metformin, sitagliptin or “no treatment.” Patients allocated to metformin will start with 500 mg twice daily, which will be slowly increased during a 6-week period to a twice daily dose of 1000 mg. Patients allocated to sitagliptin will be treated with a daily fixed dose of 100 mg. The study has been registered as NTR 3196 in The Netherlands Trial Register. Primary outcomes include percentage still on treatment, percentage of (serious) adverse events, and the baseline adjusted difference in 2-hour post-load glucose levels at 6 months.DiscussionThis study will give more information about the feasibility and safety of metformin and sitagliptin as well as the effect on 2-hour post-load glucose levels at 6 months in patients with TIA or ischemic stroke and impaired glucose tolerance.Trial registration numberNTR3196, Date of registration: 15 December 2011.

Nonfocal Symptoms in Patients with Transient Ischemic Attack or Ischemic Stroke: Occurrence, Clinical Determinants, and Association with Cardiac History

Background: Transient ischemic attacks (TIAs) accompanied by nonfocal symptoms are associated with a higher risk of cardiovascular events, in particular cardiac events. Reported frequencies of TIAs accompanied by nonfocal symptoms range from 18 to 53%. We assessed the occurrence of nonfocal symptoms in patients with TIA or minor ischemic stroke in a neurological outpatient clinic in terms of clinical determinants, cardiac history, and atrial fibrillation (AF). Methods: We included 1,265 consecutive patients with TIA or minor stroke who visited the outpatient clinic. During these visits, we systematically asked for nonfocal symptoms. Nonfocal symptoms included decreased consciousness, amnesia, positive visual phenomena, non-rotatory dizziness, and paresthesias. Relative risks for the presence of nonfocal symptoms in relation to clinical determinants, AF, and cardiac history were calculated. Results: In 243 (19%) of 1,265 patients, TIA or minor ischemic stroke was accompanied by one or more nonfocal symptoms. Non-rotatory dizziness, paresthesia, and amnesia were the most common nonfocal symptoms. In patients with an event of the posterior circulation or obesity, the qualifying TIA or minor stroke was more frequently accompanied by nonfocal symptoms, and in patients with significant carotid stenosis, nonfocal symptoms occurred less frequently. AF was related only with amnesia. Conclusion: Nonfocal symptoms are present in one out of 5 patients with TIA or ischemic stroke, in particular when located in the posterior circulation. A cardiac history or AF was not directly related to nonfocal symptoms. A heterogeneous etiology is suggested.

Comment on ‘A cervical anterior spinal artery syndrome after diagnostic blockade of the right C6-nerve root’, PJAM Brouwers et al., PAIN 91 (2001) 397–399

tible with a cauda equina lesion. I have also been aware of three similar cases following root sleeve injections of local anaesthetic and steroid. I do not know the details of the first case, but have recently been asked to comment on a case with persisting neurological sequelae after injection at C3, with hemiparesis and sensory deficit, and a further patient with urinary incontinence following root sleeve injections unilaterally at L4, L5 and S1, although it is doubtful that this was due to the injection. The anatomy of the blood supply to the cord is well described. Dommisse et al. (1980) have performed anatomical dissection of 50 human cadavers. The cord is totally dependent on the three longitudinal arterial trunks, which run from the medulla to the conus medullaris. The anterior spinal artery overlies the median sulcus of the cord, and gives off anterior perforators that supply the cord. The paired posterolateral trunks are small and tortuous, being intertwined between the posterior rootlets. The posterior perforators penetrate the cord in the company of the nerve rootlets. Ligation of the anterior vessel distal to the artery of Adamkiewicz usually leads to paraplegia in the rhesus monkey. The medullary feeder arteries supply and maintain the long arterial trunks. These are variable in number and level of supply. They arise from the segmental arteries (which supply the segmental nerves, and arise at every segmental level). There are usually more than nine (two to 17) supplying the anterior and more than 15 (six to 25) supplying the posterior trunks. The artery of Adamkiewicz (arteria radicalis anterior magna) is the largest medullary feeder and occurs on the left side in 80% of cases between T7 and L4, especially T9–T11. The intervertebral foraminae are of critical value in the blood supply of the cord, as the feeder vessels pass through the foraminae alongside the nerve root. However, Dommisse does show that there are arteri-arterial anastomoses between the segmental intervertebral arteries in the thorax. They are potential sources of alternative supply to the cord. Dommisse proposed surgical guidelines to prevent postoperative paraplegia. He stated that neither cautery nor tight plugging nor heavy retraction should be applied to the intervertebral foramen, lest a single essential feeder vessel be destroyed. Two decades on, we should heed his advice, and treat the foramen with respect. Trauma to the feeding vessels from the introduction of needles to the foramen can produce vasospasm, and the potential for consequent cord ischaemia. We have an obligation to warn our patients of the risk, however small, of such a catastrophic complication when we perform such procedures.

Comparison of outcome in stroke patients admitted during working hours vs. off-hours; a single-center cohort study

IntroductionWe aimed to disprove an in-hospital off-hour effect in stroke patients by adjusting for disease severity and poor prognostic findings on imaging.Patients and methodsOur study included 5378 patients from a single center prospective stroke registry of a large teaching hospital in the Netherlands, admitted between January 2003 and June 2015. Patients were categorized by admission time, off-hours (OH) or working hours (WH). The in-hospital mortality, 7-day mortality, unfavorable functional outcome (modified Rankin scale > 2) and discharge to home were analyzed. Results were adjusted for age, sex, stroke severity (NIHSS score) and unfavorable findings on imaging of the brain (midline shift and dense vessel sign).ResultsOverall, 2796 patients (52%) were admitted during OH, which had a higher NIHSS score [3 (IQR 2–8) vs. 3 (IQR 2–6): p < 0.01] and had more often a dense vessel sign at admission (7.9% vs. 5.4%: p < 0.01). There was no difference in mortality between the OH-group and WH-group (6.2% vs. 6.0%; p = 0.87). The adjusted hazard ratio of in-hospital mortality during OH was 0.87 (95% CI: 0.70–1.08). Analysis of 7-day mortality showed similar results. Unadjusted, the OH-group had an unfavorable outcome [OR: 1.14 (95% CI: 1.02–1.27)] and could less frequently be discharged to home [OR: 1.16 (95% CI: 1.04–1.29)], which was no longer present after adjustment.Discussion and conclusionsThe overall outcome of stroke patients admitted to a large Dutch teaching hospital is not influenced by time of admission. When studying OH effects, adjustment for disease severity and poor prognostic findings on imaging is crucial before drawing conclusions on staffing and material.