Impaired cerebrovascular reactivity may predict delayed cerebral ischemia after aneurysmal subarachnoid hemorrhage.

INTRODUCTION: Delayed cerebral ischemia (DCI) is a major cause of disability and death after aneurysmal subarachnoid hemorrhage. The literature suggests that impaired cerebrovascular reactivity (CVR) may be a predictor for DCI; still no CVR based prediction model has been developed. Increased knowledge about possible predictors of DCI can improve patient management in high-risk patients and allow for shorter hospital stay in low-risk patients. METHOD: CVR was examined in 42 patients with aneurysmal subarachnoid hemorrhage and 37 patients treated for unruptured intracranial aneurysm, using acetazolamide test with transcranial Doppler monitoring of blood flow velocities. Patients were followed for development of DCI, separated into clinical deterioration and radiographic infarction. RESULTS: For all patients, regardless of aneurysm rupture status, CVR was on average 5.5 percentage points lower on the ipsilateral side of aneurysm treatment. Patients with clinical deterioration due to DCI had lower CVR than patients without DCI, and the difference was larger on the contralateral side (33.9% vs. 49.2%). Two prediction models were constructed for clinical deterioration due to DCI. The area under the receiver operating characteristic curve was 0.82 in the model using established predictors, and 0.86 in the model that also included CVR. CONCLUSION: Our findings support the hypothesis that impaired CVR may be an independent predictor of clinical deterioration due to DCI, and may assist in identifying patients at risk after aneurysmal subarachnoid hemorrhage. Ipsilateral CVR reduction occurs in all patients after aneurysm treatment, regardless of DCI development, thus highlighting the need to evaluate ipsi- and contralateral CVR separately.

Time Course of Cerebrovascular Reactivity in Patients Treated for Unruptured Intracranial Aneurysms: A One-Year Transcranial Doppler and Acetazolamide Follow-Up Study.

BACKGROUND: Cerebrovascular reactivity (CVR) is often impaired in the early phase after aneurysmal subarachnoid hemorrhage. There is, however, little knowledge about the time course of CVR in patients treated for unruptured intracranial aneurysms (UIA). METHODS: CVR, assessed by transcranial Doppler and acetazolamide test, was examined within the first postoperative week after treatment for UIA and reexamined one year later. RESULTS: Of 37 patients initially assessed, 34 were reexamined after one year. Bilaterally, baseline and acetazolamide-induced blood flow velocities were higher in the postoperative week compared with one year later (p < 0.001). CVR on the ipsilateral side of treatment was lower in the initial examination compared with follow-up (58.9% versus 66.1%, p = 0.04). There was no difference in CVR over time on the contralateral side (63.4% versus 65.0%, p = 0.65). When mean values of right and left sides were considered there was no difference in CVR between exams. Larger aneurysm size was associated with increased change in CVR (p = 0.04), and treatment with clipping was associated with 13.8%-point increased change in CVR compared with coiling (p = 0.03). CONCLUSION: Patients with UIA may have a temporary reduction in CVR on the ipsilateral side after aneurysm treatment. The change in CVR appears more pronounced for larger-sized aneurysms and in patients treated with clipping. We recommend that ipsilateral and contralateral CVR should be assessed separately, as mean values can conceal side-differences.

Cerebrovascular reactivity after treatment of unruptured intracranial aneurysms--A transcranial Doppler sonography and acetazolamide study.

BACKGROUND: Cerebrovascular reactivity (CVR) is defined as the change in cerebral blood flow, or blood velocity, in response to a vasoactive stimulus. There is a possible association between impaired CVR and vasospasm after aneurysmal subarachnoid hemorrhage. Most studies on CVR and vasospasm have used healthy subjects as reference. However, due to potential different vascular features, CVR in persons with intracranial aneurysms may differ from CVR in healthy subjects. Therefore, our aim was to examine CVR in patients with unruptured intracranial aneurysms (UIA). METHODS: CVR was examined in 37 patients in the first postoperative week after treatment for UIA, using acetazolamide (AZ) test with transcranial Doppler monitoring of blood flow velocities. RESULTS: Mean blood flow velocity in the middle cerebral arteries was 58.5 (SD 12.8) cm/s at baseline, and 94.3 (SD 19.5) cm/s after stimulation with AZ. Mean CVR was 62.6 (SD 16.8) %. There was no significant difference when comparing right and left sides, and treated and untreated sides. A simple regression analysis suggested that CVR increased with 0.7% points for each year a patient aged (p=0.004). However, the significance disappeared in a multiple analysis (increase of 0.6% points per year, p=0.055). Other possible influencing factors (gender, smoking, hypertension, body mass index, aneurysm location and treatment modality) were not significantly associated with CVR. CONCLUSIONS: CVR in patients with UIA is not different from normal values reported in healthy subjects, and does not indicate a systemically impaired vascular system in patients with UIA. We suggest that CVR in age and gender matched healthy controls can be used as reference for persons with intracranial aneurysms.

Continuous Local Intra-Arterial Nimodipine for the Treatment of Cerebral Vasospasm.

Vasospasm (VSP) is one of the major causes for prolonged neurologic deficit in patients with aneurysmal subarachnoid hemorrhage. Few case series have reported about continuous local intra-arterial nimodipine administration (CLINA) in refractory VSP. We report our experience with CLINA in a patient with refractory cerebral VSP.

Carotid intima-media thickness--a potential predictor for rupture risk of intracranial aneurysms.

BACKGROUND: Individual assessment of rupture risk of cerebral aneurysms is challenging, and increased knowledge of predictors for aneurysm rupture is needed. Smoking and hypertension are shared risk factors for atherosclerotic disease and cerebral aneurysms, and patients with atherosclerosis have an increased prevalence of intracranial aneurysms. Carotid ultrasound with evaluation of intima-media thickness (IMT) is a non-invasive, safe, rapid, well-validated and reproducible technique for quantification of subclinical atherosclerosis and assessment of cardio- and cerebrovascular risk. Increased IMT is associated with elevated risk for ischemic stroke and myocardial infarction, but sparse data exist on carotid ultrasound findings in patients with intracranial aneurysms. AIMS: The purpose of this study was to investigate carotid IMT in patients with unruptured intracranial aneurysms (UIA) and aneurysmal subarachnoid hemorrhage (aSAH), and to assess if IMT might be associated with aneurysm rupture risk. METHODS: Patients treated for saccular aneurysms (UIA and aSAH) from February 2011 to August 2012 were included. Standardized high resolution B-mode ultrasound assessment of carotid arteries was done after aneurysm treatment, and traditional vascular risk factors were recorded. Healthy partners of young patients with ischemic stroke were used as controls. RESULTS: 69 patients treated for UIA (n=28) and aSAH (n=41) were compared with 80 controls. Mean IMT was higher in patients with aSAH (0·79 mm) than patients with UIA (0·65 mm) and controls (0·63 mm). Multiple multinomial regression analysis comparing aSAH, UIA and control groups demonstrated that IMT was the only variable predicative of aSAH compared to UIA. According to the multiple regression model, the probability of having aSAH compared to non-rupture increased by 62% for each 0·10 mm increment of mean IMT (RRR=1·62, P=0·017). Taking into account only patients harboring intracranial aneurysms, simple binary logistic regression was then applied to the UIA and aSAH groups. According to this model the risk of belonging to the aSAH group increased with higher mean IMT values (OR=1·40 per 0·10 mm increase of mean IMT, P=0·024). CONCLUSION: There is an association between IMT and intracranial aneurysm rupture status at the time of aneurysm treatment. Carotid IMT can be a potential predictor of aneurysm rupture. IMT may thus be a possible adjunct in the risk assessment of aneurysm rupture, and a helpful tool in patient risk stratification and counseling.

Shunt revisions in children--can they be avoided? Experiences from a population-based study.

BACKGROUND: Shunt failure is by far the most frequent problem in children with shunts, and most of them will experience this condition at some point in their lives. In order to identify causes of shunt failure, and to compare multi-component and one-piece shunt systems, we analyzed retrospectively all pediatric shunt procedures in our Department during an 11-year period. The study does not deal with shunt infections. METHODS: We reviewed the records of all pediatric shunting procedures between January 1986 and December 1996. RESULTS: The study included 161 children operated for hydrocephalus with a total of 431 procedures. The procedures included 124 (29%) primary insertions, 10 (2%) reinsertions and 297 (69%) revisions; 206 (69%) of the revisions were due to shunt failures, of which 74 (36%) were caused by the failure of the surgical technique (misplaced ventricular catheters, disconnected shunts, or misplaced peritoneal catheters). CONCLUSIONS: Improvement of the surgical technique may reduce the incidence of shunt failures and revisions. The results obtained in a small department like ours do not seem to differ substantially from those obtained in more specialized departments with a larger patient group. Practical measures that may reduce the risk of shunt failures are suggested.

Long-term potentiation in spinal nociceptive systems--how acute pain may become chronic.

Chronic pain is a major problem since it is difficult to treat and the understanding of the underlying neurobiology is sparse. The mechanisms underpinning the transition of acute into chronic pain remain unclear. However, long-term potentiation (LTP) in spinal nociceptive systems may be one such mechanism. Here, we briefly review the literature regarding LTP in spinal nociceptive systems including our own data on LTP in deep convergent nociceptive neurons. Furthermore, we discuss the role of this phenomenon in understanding the neurobiology of chronic pain and the possible therapeutic implications.

[Spasticity treated with selective posterior rhizotomy]. / Spastisitet behandlet med selektiv bakre rhizotomi.

BACKGROUND: Spasticity is often seen in patients with central nervous lesions. Some patients with severe spasticity are not optimally treated with physiotherapy and medication. MATERIAL AND METHODS: We present a case history of a 41-year-old woman with multiple sclerosis and severe painful spasticity in her lower limbs. Her spasticity did not respond to treatment with physiotherapy, spasmolytic medication, botulinum toxin A, intrathecal baclofen or epidural spinal cord stimulation. RESULT: The patient was treated with selective posterior rhizotomy S1-L1. Section of 60% of the rootlets on the right side and 40% on left the side resulted in a good outcome with less spasticity and pain. Finally her contractures were treated with tenotomy and myotomy, also with good functional result. INTERPRETATION: Patients suffering from severe painful spasticity and who do not respond to physiotherapy in combination with other spasmolytic medication should be considered for surgical treatment. In some patients posterior rhizotomy is the treatment of choice.

Cellular memory in spinal nociceptive circuitry.

Besides transmitting and processing, neurons may also store information for prolonged periods of time (e.g. by use-dependent change in synaptic strength). In 1966 long-term potentiation (LTP) of synaptic transmission was discovered in the hippocampus, an area implicated in learning and memory. Recent studies show that similar mechanisms apply to pain pathways, at least in the spinal cord, and may account for some forms of clinical problems like hyperalgesia, allodynia, and deafferentation pain states, such as phantom pain. In this review, we briefly summarize key aspects of synaptic plasticity known from the brain and in the spinal cord. Then we describe and discuss related changes in spinal nociceptive neurons based on results from our own laboratory.

Increased spinal N-methyl-D-aspartate receptor function after 20 h of carrageenan-induced inflammation.

Spinal N-methyl-D-aspartate (NMDA) receptors are thought to be important in states of central hyperexcitability induced by e.g. inflammation or painful neuropathies. The carrageenan model of inflammatory pain has been and still is widely used as is the NMDA receptor antagonist 2-amino-5-phosphonopentanoic acid (AP5) to investigate NMDA receptor function. Here we present two novel findings using electrophysiological technique: the NMDA receptor function in the spinal cord is increased following 20 h of carrageenan-induced inflammation and further that only the D-isomer of AP5 is active in the spinal cord. Exogenous NMDA (0.5 and 5 nmol) applied onto the dorsal spinal cord produced a significantly greater facilitation and D-AP5 (1.25 micromol) a significantly greater inhibition of the C-fibre evoked response of the wide dynamic range (WDR) neurones studied in carrageenan (20 h after injection) compared to control rats. The present and two recent studies suggest central changes are different and possibly greater in the later (20 h) compared to the earlier (2-6 h) phase of carrageenan-induced inflammation. In conclusion, 20 h of carrageenan-induced inflammation increases the function of spinal NMDA receptor involved in nociceptive transmission and in addition the D-isomer of AP5 should be used when NMDA receptor antagonism is wanted in the spinal cord.

Dorsal horn NMDA receptor function is changed after peripheral inflammation.

The N-methyl-D-aspartic acid (NMDA) receptor antagonist D, L-2-amino-5-phosphonopentanoic acid (AP5) caused a stronger inhibition of wind-up in single wide dynamic range (WDR) neurons after carrageenan inflammation compared with control neurons without inflammation in the receptive field. This indicates that even a short period (2.5 h) of inflammation induces changes in the function of NMDA receptors. The drug effect was also studied in separate control experiments with few wind-up inducing stimulus trains and little nociceptive input prior to baseline recordings. In these control experiments all evoked responses were reduced by the drug, but the wind-up was significantly increased. A wind-up increase after NMDA receptor antagonism has been reported in two previous studies. Thus, other mechanisms than NMDA receptor stimulation may be more important for the wind-up in not sensitized dorsal horn neurons. As for long-term potentiation, it seems that NMDA receptor antagonists have an increased effect after sensitization. Thus, sensitized and not sensitized dorsal horn neurons may respond differently to an NMDA receptor active drug. In rats nerve stimulation and halothane anaesthesia induced larger evoked responses to afferent stimulation than cutaneous stimulation and urethane anaesthesia, the AP5 effect was however similar.

Natural noxious stimulation can induce long-term increase of spinal nociceptive responses.

It is conceivable that plasticity in pain control systems and chronic pain may be due to mechanisms similar to learning. Long-term potentiation (LTP) in the hippocampus is often studied as a model of learning and memory. It has recently been shown that long-term excitation may be induced in single wide dynamic range (WDR) neurones in the spinal dorsal horn of rats after tetanic stimulation to the sciatic nerve. The present study shows that similar long-term changes can also be induced by a severe natural stimulus. Single unit extracellular recordings were made in urethane anaesthetized rats and the firing responses of WDR neurones evoked by a single electrical stimulus to the peripheral nerve were recorded every 4 min. After repeated crushing of tissue (including bone) corresponding to the receptive field of the WDR neurones (the conditioning stimulus) followed by a proximal total peripheral nerve block, the C-fibre evoked responses were increased (P < 0.001) for a 3 h observation period compared with baseline responses and control animals. In control animals the nerve block was applied before the conditioning stimulus. We suggest that a long-term increase of the excitability of WDR neurones may be important for the development of long lasting and chronic pain disorders after an acute but severe noxious stimulus.