Frans Bruyninckx

Intensive Insulin Therapy in Mixed Medical/Surgical Intensive Care Units: Benefit Versus Harm

Intensive insulin therapy (IIT) improves the outcome of prolonged critically ill patients, but concerns remain regarding potential harm and the optimal blood glucose level. These questions were addressed using the pooled dataset of two randomized controlled trials. Independent of parenteral glucose load, IIT reduced mortality from 23.6 to 20.4% in the intention-to-treat group (n = 2,748; P = 0.04) and from 37.9 to 30.1% among long stayers (n = 1,389; P = 0.002), with no difference among short stayers (8.9 vs. 10.4%; n = 1,359; P = 0.4). Compared with blood glucose of 110–150 mg/dl, mortality was higher with blood glucose >150 mg/dl (odds ratio 1.38 [95% CI 1.10–1.75]; P = 0.007) and lower with <110 mg/dl (0.77 [0.61–0.96]; P = 0.02). Only patients with diabetes (n = 407) showed no survival benefit of IIT. Prevention of kidney injury and critical illness polyneuropathy required blood glucose strictly <110 mg/day, but this level carried the highest risk of hypoglycemia. Within 24 h of hypoglycemia, three patients in the conventional and one in the IIT group died (P = 0.0004) without difference in hospital mortality. No new neurological problems occurred in survivors who experienced hypoglycemia in intensive care units (ICUs). We conclude that IIT reduces mortality of all medical/surgical ICU patients, except those with a prior history of diabetes, and does not cause harm. A blood glucose target <110 mg/day was most effective but also carried the highest risk of hypoglycemia.

Clinical review: Critical illness polyneuropathy and myopathy

Critical illness polyneuropathy (CIP) and myopathy (CIM) are major complications of severe critical illness and its management. CIP/CIM prolongs weaning from mechanical ventilation and physical rehabilitation since both limb and respiratory muscles can be affected. Among many risk factors implicated, sepsis, systemic inflammatory response syndrome, and multiple organ failure appear to play a crucial role in CIP/CIM. This review focuses on epidemiology, diagnostic challenges, the current understanding of pathophysiology, risk factors, important clinical consequences, and potential interventions to reduce the incidence of CIP/CIM. CIP/CIM is associated with increased hospital and intensive care unit (ICU) stays and increased mortality rates. Recently, it was shown in a single centre that intensive insulin therapy significantly reduced the electrophysiological incidence of CIP/CIM and the need for prolonged mechanical ventilation in patients in a medical or surgical ICU for at least 1 week. The electrophysiological diagnosis was limited by the fact that muscle membrane inexcitability was not detected. These results have yet to be confirmed in a larger patient population. One of the main risks of this therapy is hypoglycemia. Also, conflicting evidence concerning the neuromuscular effects of corticosteroids exists. A systematic review of the available literature on the optimal approach for preventing CIP/CIM seems warranted.

Value of somatosensory and motor evoked potentials in predicting arm recovery after a stroke

OBJECTIVES Prediction of motor recovery in the arm in patients with stroke is generally based on clinical examination. However, neurophysiological measures may also have a predictive value. The aims of this study were to assess the role of somatosensory (SSEPs) and motor (MEPs) evoked potentials in the prediction of arm motor recovery and to determine whether these measures added further predictive information to that gained from clinical examination. METHODS Sixty four patients who had had a stroke and presented with obvious motor deficit of the arm were examined in terms of three clinical variables (motor performance, muscle tone, and overall disability) and for SSEPs and MEPs. Clinical and neurophysiological examinations were done at entry to the study (2 to 5 weeks poststroke), and at about 2 months after stroke. Further clinical follow up was conducted at 6 and 12 months after stroke. RESULTS Neurophysiological measures made in the acute phase were of little use alone in predicting motor recovery of the arm at 2, 6, and 12 months after stroke. At 2 months, the absence of SSEPs and MEPs indicated a very poor outcome. Conversely, if the responses were preserved, a great variation in motor outcome was found. Multiple regression analysis showed that the addition of SSEPs and MEPs to the clinical examination increased the possibility of predicting arm recovery in the long term. In the acute phase, the combination of the motor score and SSEPs were best able to predict outcome. The long term outcome based on variables taken at 2 months, was best predicted through incorporating the three clinical measures and MEPs. CONCLUSIONS Neurophysiological measures alone are of limited value in predicting long term outcome. However, predictive accuracy is substantially improved through the combined use of both of these measures and clinical variables.

Muscle atrophy and preferential loss of myosin in prolonged critically ill patients

Objective:Muscle weakness contributes to prolonged rehabilitation and adverse outcome of critically ill patients. Distinction between a neurogenic and/or myogenic underlying problem is difficult using routine diagnostic tools. Preferential loss of myosin has been suggested to point to a myogenic component. We evaluated markers of muscle atrophy and denervation, and the myosin/actin ratio in limb and abdominal wall skeletal muscle of prolonged critically ill patients and matched controls in relation to insulin therapy and known risk factors for intensive care unit-acquired weakness. Design:Secondary analysis of two large, prospective, single-center randomized clinical studies. Setting:University hospital surgical and medical intensive care unit. Patients:Critically ill patients and matched controls. Interventions:Intensive care unit patients had been randomized to blood glucose control to 80–110 mg/dL with insulin infusion or conventional glucose management, where insulin was only administered when glucose levels rose above 215 mg/dL. Measurements and Main Results:As compared with controls, rectus abdominis and vastus lateralis muscle of critically ill patients showed smaller myofiber size, decreased mRNA levels for myofibrillar proteins, increased proteolytic enzyme activities, and a lower myosin/actin ratio, virtually irrespective of insulin therapy. Increased forkhead box O1 action may have played a role. Most alterations were more severe in patients treated with corticosteroids. Duration of corticosteroid treatment, independent of duration of intensive care unit stay or other risk factors, was a dominant risk factor for a low myosin/actin ratio. The immature acetylcholine receptor subunit &ggr; messenger RNA expression was elevated in vastus lateralis, independent of the myosin/actin ratio. Conclusions:Both limb and abdominal wall skeletal muscles of prolonged critically ill patients showed downregulation of protein synthesis at the gene expression level as well as increased proteolysis. This affected myosin to a greater extent than actin, resulting in a decreased myosin/actin ratio. Muscle atrophy was not ameliorated by intensive insulin therapy, but possibly aggravated by corticosteroids.

Functional recovery of diaphragm paralysis: A long-term follow-up study

BACKGROUND Long-term functional outcome of diaphragm paralysis is largely unknown. METHODS A retrospective study was conducted in 23 consecutive patients (21 males, 56+/-9 years) with uni- or bilateral diaphragm paralysis to examine whether functional respiratory recovery can be predicted from the compound motor action potential (CMAP) of the diaphragm at the time of diagnosis. Pulmonary function and CMAP were evaluated at baseline and at follow-up. CMAP amplitude and latency were recorded by surface electromyography with percutaneous electrical stimulation of the phrenic nerve. Patients were followed for (median) 15 months up to 131 months (range 5-131). Functional respiratory recovery was defined as an increase in forced vital capacity > 400 ml. RESULTS Functional recovery occurred in 43% of the patients after 12 months (10 out of 23) and in 52% after 24 months (12 out of 23). Type and etiology of paralysis did not influence recovery. CMAP, anthropometric characteristics and baseline pulmonary function did not predict functional respiratory recovery. Whether respiratory muscle training improved pulmonary function is uncertain. Moreover, it did not result in a greater percentage functional respiratory recovery. Relapse after an initial improvement was observed in 26% of the patients. CONCLUSIONS The present study indicates that functional recovery of diaphragm paralysis is difficult to predict and may occur years after the onset of the paralysis.

How does brain activation differ in children with unilateral cerebral palsy compared to typically developing children, during active and passive movements, and tactile stimulation? An fMRI study.

The aim of the functional magnetic resonance imaging (fMRI) study was to investigate brain activation associated with active and passive movements, and tactile stimulation in 17 children with right-sided unilateral cerebral palsy (CP), compared to 19 typically developing children (TD). The active movements consisted of repetitive opening and closing of the hand. For passive movements, an MRI-compatible robot moved the finger up and down. Tactile stimulation was provided by manually stroking the dorsal surface of the hand with a sponge cotton cloth. In both groups, contralateral primary sensorimotor cortex activation (SM1) was seen for all tasks, as well as additional contralateral primary somatosensory cortex (S1) activation for passive movements. Ipsilateral cerebellar activity was observed in TD children during all tasks, but only during active movements in CP children. Of interest was additional ipsilateral SM1 recruitment in CP during active movements as well as ipsilateral S1 activation during passive movements and tactile stimulation. Another interesting new finding was the contralateral cerebellum activation in both groups during different tasks, also in cerebellar areas not primarily linked to the sensorimotor network. Active movements elicited significantly more brain activation in CP compared to TD children. In both groups, active movements displayed significantly more brain activation compared to passive movements and tactile stimulation.

Spinal somatosensory evoked potentials after epidural isoproterenol in awake sheep

PurposeThe use of 10–15 μg epinephrine as an epidural test-dose is controversial. Isoproterenol would be a better alternative. However before 5μg isoproterenol can be incorporated in an epidural test-dose, neurotoxicological studies have to be performed. The present study was designed to assess spinal somatosensory evoked potentials (spinal SSEP) before and after epidural isoproteronol.MethodsSpinal SSEPs were recorded before, 30 min after, and 72 hr after 50 μg isoproterenol were given epidurally (L3–4) to six chronically instrumented awake sheep. The spinal SSEPs after epidural (L3–4 administration of 15 ml lidocaine 2% were used to evaluate the model. The SSEPs were generated by transcutaneous stimulation of the sciatic nerve in the thigh. Spinal SSEPs were recorded directly from the spinal cord at vertebra T12 using a monopolar epidural electrode referenced to a subcutaneous needle electrode in the adjacent paraspinal area.ResultsThirty minutes and 72 hr after epidural injection of 50 μg isoproterenol the latency and the amplitude of the SSEP waves were similar to baseline values. After lidocaine, no SSEPs could be generated in three sheep while in three sheep the latency of wave 2 (W2) was prolonged and the amplitude diminished.ConclusionAdministration of epidural isoproterenol did not affect spinal SSEPs in this study indicating an absence of neurotoxic side effects.RésuméObjectifL’utilisation de 10–15 μg d’épinéphrine comme dose-test de l’anesthésie épidurale est contestée. Lisoprotérénol devrait être une meilleure solution de rechange. Cependant, avant d’incorporer 5 μg d’isoprotérénol à une dose-test épidurale, il faut effectuer des études de neurotoxicité. L’étude actuelle visait à mesurer les potentiels évoqués somatosentoriels (SS) spinaux avant et après de l’isoprotérénol épidural.MéthodesLes SSEP spinaux ont été enregistrés avant, 30 min après et 72 h après l’administration épidurale de 50μg d’isoprotérénol (L3-L4) à six préparations de moutons éveillés. Les SSEP spinaux enregistrés après l’administration de 15 ml de lidocaïne 2% ont servi à valider le modèle. Les SSEP ont été générés par stimulation transcutanée du nerf sciatique au niveau de la cuisse. Les SSEP spinaux ont été enregistrés directement sur la moelle au niveau de T12 avec une électrode unipolaire ; l’électrode de référence était une aiguille sous-cutanée insérée dans la région paraspinale adjacente.RésultatsTrente minutes et 72 h après l’injection épidurale de 50 μg d’ isoprotérénol, la latence et l’amplitude des ondes SSEP étaient identiques aux valeurs initiales. Après la lidocaïne, les SSEP ne pouvaient être générés chez trois moutons alors que chez les trois autres, la latence de l’Onde 2 (W2) était prolongée et son amplitude diminuée.ConclusionPendant cette étude, l’administration d’isoprotérénol épidural n’a pas affecté les SSEP spinaux, ce qui démontre l’absence d’effets neurotoxiques.

Electromyographic Abnormalities Associated with Symptomatic Sacral Tarlov Cysts

Tarlov or perineural cysts (TC) are commonly overlooked as a cause of sacral and ischial pain, and urogenital and bowel problems. TC can be seen on MRI, but are often considered asymptomatic. This is especially true for smaller cysts. Moreover, there are only few diagnostic characteristics that can be used to confirm that the cysts are the cause of the symptoms. As a consequence, a lot of controversy remains regarding the clinical importance of TC. Because of this underdiagnosed condition, patients often suffer for several years from unrecognized chronic neuropathic pain and neurological conditions. In this article, case reports of three patients with giant and smaller symptomatic sacral cysts are presented, in which electromyographic testing was performed to demonstrate nerve damage.

Fibromyalgia and unexplained widespread pain: The idiopathic cerebrospinal pressure dysregulation hypothesis

Fibromyalgia (FM) is a debilitating, widespread pain disorder that is assumed to originate from inappropriate pain processing in the central nervous system. Psychological and behavioral factors are both believed to underlie the pathogenesis and complicate the treatment. This hypothesis, however, has not yet been sufficiently supported by scientific evidence and accumulating evidence supports a peripheral neurological origin of the symptoms. We postulate that FM and several unexplained widespread pain syndromes are caused by chronic postural idiopathic cerebrospinal hypertension. Thus, the symptoms originate from the filling of nerve root sleeves under high pressure with subsequent polyradiculopathy from the compression of the nerve root fibers (axons) inside the sleeves. Associated symptoms, such as bladder and bowel dysfunction, result from compression of the sacral nerve root fibers, and facial pain and paresthesia result from compression of the cranial nerve root fibers. Idiopathic Intracranial Hypertension, Normal Pressure Hydrocephalus and the clinical entity of symptomatic Tarlov cysts share similar central and peripheral neurological symptoms and are likely other manifestations of the same condition. The hypothesis presented in this article links the characteristics of fibromyalgia and unexplained widespread pain to cerebrospinal pressure dysregulation with support from scientific evidence and provides a conclusive explanation for the multitude of symptoms associated with fibromyalgia.

Electromyography and A Review of the Literature Provide Insights into the Role of Sacral Perineural Cysts in Unexplained Chronic Pelvic, Perineal and Leg Pain Syndromes

Objective: The clinical entity “Symptomatic Tarlov Cysts” is a highly under reported condition. We aimed to perform an electrophysiologic evaluation in patients with Tarlov cysts to determine whether the cysts create electrical abnormalities that could translate into clinical symptoms. The findings are correlated with the data currently available in the literature. Methods: Thirty patients with unexplained pelvic, sacral, perineal and/or leg pain who harbored small and/or large Tarlov cysts were selected at an outpatient clinic for physical medicine in musculoskeletal disorders. An MRI of the lumbosacral spine of each patient was reviewed. An experienced physiatrist acquired information related to pain and paresthesia in addition to bladder, bowel and sphincter symptoms. An expert electrophysiologist performed nerve conduction and electromyography studies on the patient’s legs and the pelvic floor. A review of the case reports on Tarlov cysts was performed. The symptoms of the patients in the study were compared with the symptoms reported in reviews and case reports. Results: In all cases, the presence of Tarlov cysts was associated with sensory neuron symptoms, such as pain and paresthesia, and with bladder, bowel, sexual, and/or sphincter complaints. In all cases, electromyography documented axonal damage in multiple lumbar and sacral nerve root myotomes. Conclusion: Symptomatic Tarlov cysts clinically and electrophysiologically represent a progressive chronic cauda equine syndrome. In patients with intractable sacral, perineal, pelvic or leg pain, symptomatic Tarlov cysts should be included in the differential diagnosis.