Cerebrospinal fluid drainage and thoracic endovascular aneurysm repair.

Spinal cord complications including paraplegia and partial neurologic deficits remain a frequent problem during repair of descending thoracic or thoracoabdominal aortic aneurysms. Effective prevention of this dreaded complication is of paramount importance. Among the many adjuncts that have been proposed to prevent spinal cord complications, spinal fluid drainage is one that has been used by numerous teams. The aim of this review is to answer the following question: does spinal fluid drainage afford spinal cord protection during both open and endovascular repair of thoracic or thoracoabdominal aortic aneurysms?

Heroin-induced acute myelopathy with extreme high levels of CSF glial fibrillar acidic protein indicating a toxic effect on astrocytes.

A man aged 33 years with previous heroin substance abuse was found unconscious lying in a bush. The patient had been without heroin for some time but had just started to use intravenous heroin again, 0.5-2 g daily. The patient had almost complete paraplegia and a sensory loss for all modalities below the mamillary level and a urine retention of 1.5 L. Acute MRI of the spine revealed an expanded spinal cord with increased intramedullary signal intensity, extending from C7-T9. The cerebrospinal fluid showed extremely high levels of nerve injury markers particularly glial fibrillar acidic protein (GFAP): 2 610 000/ng/L (ref. <750). The patient was empirically treated with intravenous 1 g methylprednisolone daily for 5 days and improved markedly. Very few diseases are known to produce such high levels of GFAP, indicating a toxic effect on astrocytes. Measuring GFAP could possibly aid in the diagnosis of heroin-induced myelopathy.

Intraoperative Changes in Cerebrospinal Fluid Gas Tensions Reflect Paraplegia During Thoracoabdominal Aortic Surgery: A Proof-of-Principle Study.

BACKGROUND: In this study, gas tensions in cerebrospinal fluid (CSF) were prospectively evaluated as intraoperative markers for the detection of neurological deficits. METHODS: Spinal fluid, serum, and heart lung machine (HLM) perfusate were monitored for gas tensions (po 2/pCo 2) and related parameters (pH, lactate, and glucose) during thoracoabdominal aortic repair and correlated with perioperative neurological examination and electrophysiological testing. RESULTS: Forty-seven patients were assessed for the study, and 40 consecutive patients were finally included. The patients were divided into 3 groups: group A (23 patients, 57.5%): no clinical or laboratory signs of neurological damage; group B (14 patients, 35%) who developed subclinical deficits; and group C (3 patients, 7.5%) who had paraplegia. Significant intraoperative changes in CSF gas tensions were observed with postoperative paraplegia. Glucose ratio between serum and CSF showed higher variability in group C, confirming a damage of the blood-brain barrier (BBB). CONCLUSION: Major neurological damage is reflected by early changes in CSF gas tensions and glucose variability, suggesting damage of the BBB in these patients.

Novel application of acetazolamide to reduce cerebrospinal fluid production in patients undergoing thoracoabdominal aortic surgery.

OBJECTIVES: Paraplegia is a rare but devastating complication, which may follow thoracoabdominal aortic surgery. Many adjuncts have been developed to reduce this risk including cerebrospinal fluid (CSF) drainage. Acetazolamide (carbonic anhydrase inhibitor) is a drug used to counteract mountain sickness and one of its effects is to reduce CSF production. Here, we report its first postoperative application in thoracoabdominal surgery with the aim of reducing cerebrospinal cord perfusion pressure and reducing risk of paraplegia. METHODS: We retrospectively reviewed 6 patients who have been treated with this drug between 2011 and 2012 who were undergoing thoracoabdominal aortic surgery. Our indications were decided to include: (i) patients in whom a spinal drain could not be positioned; (ii) patients with blood-stained CSF; (iii) patients in whom the volume of CSF drained was outside guidelines; (iv) patients in whom CSF pressure was elevated; (v) patients with excessive vasopressor usage and (vi) patients with postoperative neurological dysfunction as measured by motor-evoked potentials or clinical examination. All were given 500 mg intravenous acetazolamide, not more than eight hourly, for a duration dependent on response. RESULTS: In the 6 patients, 2 received a single dose of the drug and responded by an immediate drop in intracranial pressure (ICP) pressure. Of the 4 who received multiple doses of the drug, 1 had an immediate decline in ICP after each of the first six doses, while 3 had no discernable response. CONCLUSIONS: This is the first report of the efficacy of acetazolamide in reducing CSF production and lowering ICP during thoracoabdominal aortic surgery. We believe that its use will be beneficial in the 6 patient groups described. Our experience suggests there are 'responders' and 'non-responders', the characteristics of whom are yet to be defined. Its efficacy in reducing not just CSF volume and ICP but also clinically relevant morbidity such as paraplegia, is the subject of a planned randomized controlled trial. This report serves to raise awareness of the possible efficacy of this drug when normal management strategies are limited or exhausted.

Successful reversal of immediate paraplegia associated with repair of acute Type A aortic dissection using cerebrospinal fluid drainage.

We present a case of a 49-year old man who suffered from immediate paraplegia upon awakening from anaesthesia after surgery for acute aortic dissection Type A. A catheter was promptly inserted into the spinal canal for cerebrospinal fluid drainage, and the cerebrospinal fluid pressure was maintained <10 cmH2O. Although magnetic resonance imaging showed extensive spinal cord ischaemia, the patient gradually recovered from the paraplegia and was able to walk by himself after rehabilitation. In some cases, cerebrospinal fluid drainage can be effective for the treatment of immediate postoperative spinal cord damage.

Update on molecular characterization of coxsackievirus B5 strains.

Among Coxsackie B viruses, Coxsckievirus B5 is one of the most predominant serotypes in human, it is frequently associated with cases of neurological diseases, epidemics of meningitis and is a common cause of cardiomyopathy and diabetes. In the present study 27 isolates of Coxsackievirus B5 from North Africa, obtained from cerebrospinal fluid and stool samples of healthy individuals, patients with acute flaccid paralysis or aseptic meningitis were investigated by partial sequencing in the 5' half of the VP1 region and compared to the up-to-date published Coxsackievirus B5 sequences in the same genomic region. Four distinct genomic groups and ten different clusters were individualized. Most of the isolates from Algeria and Tunisia belonged to two clusters. For both, the sequences from North Africa clustered mainly with sequences from European countries, the majority isolated recently during the 2000s. The analysis of the alignment of amino-acids sequences in the VP1 gene revealed four major substitutions in strains from different clusters, we also noticed changes in the BC-loop region; this region is associated with viral antigenicity. This study permit to better identify circulating Coxsackievirus B5 strains throughout the world and their genetic relationship. The protein analysis showed changes that could imply some antigenic significance. J. Med. Virol. 83:1247-1254, 2011. © 2011 Wiley-Liss, Inc.

Paraplegia following elective endovascular repair of abdominal aortic aneurysm: reversal with cerebrospinal fluid drainage.

Paraplegia secondary to spinal cord ischaemia is a rare but devastating complication of abdominal aortic aneurysm repair. We report a case of paraplegia following elective endovascular repair of an infrarenal aortic aneurysm. A cerebrospinal fluid (CSF) drain was immediately inserted and resulted in full neurological recovery. This case highlights the fact that endovascular techniques are prone to similar complications as open surgery, and the importance of prompt cerebrospinal fluid drainage in cases of spinal cord ischaemia.

Multilevel somatosensory evoked potentials and cerebrospinal proteins: indicators of spinal cord injury in thoracoabdominal aortic aneurysm surgery.

OBJECTIVE: Multilevel somatosensory evoked potentials (SSEP) and the release of biochemical markers in cerebrospinal fluid (CSF) were investigated to identify patients with spinal cord ischemia during thoracoabdominal aortic repair and/or a vulnerable spinal cord during the postoperative period. METHODS: Thirty-nine consecutive patients undergoing elective aneurysm repair using distal aortic perfusion and cerebrospinal fluid drainage were studied. Continuous SSEP were monitored using nerve stimulation of the right and left posterior tibial nerves with signal recording at the level of both common peroneal nerves, the cervical cord and at the cortical level. CSF concentrations of the markers glial fibrillary acidic protein (GFAp), the light subunit of neurofilament triplet protein (NFL), and S100B were determined at different time points from before surgery until 3 days postoperatively. RESULTS: SSEP indicated spinal cord ischemia in two patients leading to additional intercostal artery reattachments. In one of them the signal loss was permanent and the patient woke up with paraplegia. In the other the signal returned but the patient later developed delayed paraplegia. Three patients without SSEP indications of spinal cord ischemia during surgery later developed delayed paraplegia. The patients with spinal cord symptoms had significant increases, during the postoperative period of CSF biomarkers GFAp (571-fold), NFL (14-fold) and S100B (18-fold) compared to asymptomatic patients. GFAp increased before or in parallel to onset of symptoms in the patients with delayed paraplegia. CONCLUSIONS: Peroperative multilevel SSEP has a high specificity in detecting spinal cord ischemia but does not identify all patients with a postoperative vulnerable spinal cord. Biochemical markers in CSF increase too late for intraoperative monitoring but GFAp is promising for identifying patients at risk for postoperative delayed paraplegia.

Biochemical markers of cerebrospinal ischemia after repair of aneurysms of the descending and thoracoabdominal aorta.

OBJECTIVE: To investigate the clinical potential of several markers of spinal cord ischemia in cerebrospinal fluid (CSF) and serum during aneurysm repair of the descending thoracic or thoracoabdominal aorta. DESIGN: Observational study of consecutive patients. Nonblinded, nonrandomized. SETTING: University hospital thoracic surgical unit. PARTICIPANTS: Eleven consecutive elective patients. INTERVENTIONS: Distal extracorporeal circulation and maintenance of CSF pressure <10 mmHg until intrathecal catheter removal. MEASUREMENTS AND MAIN RESULTS: CSF and serum levels of S100B (and its isoforms S100A1B and S100BB), neuronal-specific enolase (NSE), and the CSF levels of glial fibrillary acidic protein (GFAp) and lactate were determined. Two patients had postoperative neurologic deficit. One with a stroke showed a 540-fold increased GFAp, a 6-fold NSE, and S100B increase in CSF. One with paraplegia had a 270-fold increase in GFAp, a 2-fold increase in NSE, and 5-fold increased S100B in CSF. One patient without deficit increased GFAp 10-fold, NSE 4-fold, and S100B 23-fold in CSF. CSF lactate increased >50% in 6 of 9 patients without neurologic deficit. Serum S100B increased within 1 hour of surgery in all patients without any concomitant increase in CSF. S100A1B was about 70% of total S100B in both serum and CSF in patients with or without neurologic defects. S100B in CSF increased 3-fold in 3 of 9 asymptomatic patients. CONCLUSIONS: In patients with neurologic deficit, GFAp in CSF showed the most pronounced increase. Biochemical markers in CSF may increase without neurologic symptoms. There is a significant increase in serum S100B from surgical trauma alone without any increase in CSF.

Psychomotor retardation, spastic paraplegia, cerebellar ataxia and dyskinesia associated with low 5-methyltetrahydrofolate in cerebrospinal fluid: a novel neurometabolic condition responding to folinic acid substitution.

INTRODUCTION: Normal brain development and function depend on the active transport of folates across the blood-brain barrier. The folate receptor-1 (FR 1) protein is localized at the basolateral surface of the choroid plexus, which is characterized by a high binding affinity for circulating 5-methyltetrahydrofolate (5-MTHF). PATIENTS AND METHODS: We report on the clinical and metabolic findings among five children with normal neurodevelopmental progress during the first four to six months followed by the acquisition of a neurological condition which includes marked irritability, decelerating head growth, psychomotor retardation, cerebellar ataxia, dyskinesias (choreoathetosis, ballism), pyramidal signs in the lower limbs and occasional seizures. After the age of six years the two oldest patients also manifested a central visual disorder. Known disorders have been ruled out by extensive investigations. Cerebrospinal fluid (CSF) analysis included determination of biogenic monoamines, pterins and 5-MTHF. RESULTS: Despite normal folate levels in serum and red blood cells with normal homocysteine, analysis of CSF revealed a decline towards very low values for 5-methyltetrahydrofolate (5-MTHF), which suggested disturbed transport of folates across the blood-brain barrier. Genetic analysis of the FR 1 gene revealed normal coding sequences. Oral treatment with doses of the stable compound folinic acid (0.5-1 mg/kg/day Leucovorin(R)) resulted in clinical amelioration and normalization of 5-MTHF values in CSF. CONCLUSION: Our findings identified a new condition manifesting after the age of 6 months which was accompanied by low 5-MTHF in cerebrospinal fluid and responded to oral supplements with folinic acid. However, the cause of disturbed folate transfer across the blood-brain barrier remains unknown.

The relationship between evoked potentials and measurements of S-100 protein in cerebrospinal fluid during and after thoracoabdominal aortic aneurysm surgery.

OBJECTIVE: This study was performed to correlate the changes in concentration of S-100 protein in the cerebrospinal fluid (CSF) during and after thoracoabdominal aortic aneurysm (TAAA) surgery with the results of somatosensory and motor evoked potential monitoring. METHODS: The study was designed as a prospective study at St Antonius Hospital in Nieuwegein, The Netherlands. The participants were 19 patients who were undergoing elective TAAA surgery. CSF samples for analysis of S-100 protein were drawn after the induction of anesthesia, during the cross-clamp period of the critical aortic segment, after 5 minutes of reperfusion of this segment, during the closure of the skin, and 24 hours after the closure of the skin. In all the patients, continuous intraoperative recording of myogenic motor potentials evoked by transcranial electrical stimulation (tcMEP) and somatosensory potentials evoked by stimulation of the posterior tibial nerve took place to monitor the integrity of the spinal cord. The operative technique consisted of staged or sequential clamping to maximize the beneficial effect of the distal perfusion by the left heart bypass, continuous CSF drainage to keep the CSF pressure below 10 mm Hg, and moderate hypothermia (32 degrees C rectal temperature). We correlated the measured concentrations of S-100 protein in CSF with the results of evoked potential monitoring during surgery and the number of intercostals reimplanted and oversewn. RESULTS: In all the patients, the concentration of S-100 protein was increased in CSF. The highest concentration of S-100 protein was found in the CSF sample taken 5 minutes after reperfusion of the critical aortic segment. There was a good (negative) correlation between the changes in S-100 protein in CSF and the changes in motor evoked potential monitoring during the cross-clamp period. The best (negative) correlation was detected between the S-100 protein elevation in the CSF sample drawn 5 minutes after reperfusion and the tcMEP amplitude reduction during clamping (r = -0.73; P =.007). No relation was found between the S-100 protein dynamics in CSF and somatosensory evoked potential monitoring. A positive (r = 0.58; P =.05) correlation was found between the change in tcMEP amplitude during clamping and the number of reattached intercostals. A moderate to good (r = -0.5 to -0.7; P <.05) correlation between the number of reattached intercostals and the changes in S-100 protein concentration in CSF during TAAA surgery was found. Our data show that transient elevations in S-100 protein after cross clamping are larger in those patients with marked decrease in tcMEP from baseline during the cross-clamp period. CONCLUSION: A correlation is shown between an increasing concentration of S-100 protein in CSF and a reduction in tcMEP amplitude during cross clamping of the aorta. The S-100 protein in CSF seems to be a marker of potential clinical value in the evaluation of the effects of procedures to detect and reduce spinal cord ischemia.

Increase of the serotonin metabolite, 5-hydroxyindoleacetic acid, in cerebro-spinal fluid and spinal cord of bovines affected with the paraplegic syndrome.

The paraplegic syndrome of bovines is a condition characterized by impairment of locomotion, hypoalgesia and finally death within 72 h. The pathogenesis of the syndrome has not been established. In the present work we determined the levels of monoamines and their metabolites in cerebro-spinal fluid and spinal cord of affected animals in order to investigate the functional state of these neurotransmitters. The content of the main metabolite of serotonin, 5-hydroxyindoleacetic acid, was elevated in the cerebro-spinal fluid and in the gray matter of the spinal cord of paraplegic bovines. Serotonin content in the spinal cord did not differ with respect to control animals, but was decreased in the cerebro-spinal fluid of affected animals. Modifications in the noradrenergic system were also observed, but were less consistent, for which reason further studies are needed. These observations indicate an increase in the turnover rate of serotonin in the paraplegic syndrome. The meaning of the described alterations is unknown at the moment.

Incriase of the serotonin metabolite, 5-hydroxyindoleacetic acid, in cerebro-spinal fluid and spinal cord of bovines affected with the paraplegic syndrome

The paraplegic syndrome of bovines is a condition characterized by impairment of locomotion, hypoalgesia and finally death within 72 h. The pathogenesis of the syndrome has not been established. In the present work we determined the levels of monoamines and their metabolites in cerebro-spinal fluid and spinal cord of affected animals in order to investigate the functional state of these neurotransmitters. The content of the main metabolite of serotonin, 5-hydroxyindoleacetic acid, was elevated in the cerebro-spinal fluid and in the gray matter of the spinal cord of paraplegic bovines. Serotonin content in the spinal cord did not differ with respect to control animals, but was decreased in the cerebro-spinal fluid of affected animals. Modifications in the noradrenergic system were also observed, but were less consistent, for which reason further studies are needed. These observations indicate an increase in the turnover rate of serotonin in the paraplegic syndrome. The meaning of the described alterations is unknown at the moment

A prospective randomized study of cerebrospinal fluid drainage to prevent paraplegia after high-risk surgery on the thoracoabdominal aorta.

This article is concerned with the study of the effect of several variables, principally that of cerebrospinal fluid drainage, on the incidence of neurologic deficit in a prospective randomized series of patients with extensive aneurysms of the descending thoracic and abdominal aorta (thoracoabdominal type I and II). Forty-six patients had cerebrospinal fluid drainage, and 52 were controls, with a total of 98 available for study. Cerebrospinal fluid pressure was continuously monitored in the former group and pressure maintained less than or equal to 10 mm Hg in 20, less than or equal to 15 mm Hg in 20, and greater than 15 mm Hg in 6 patients during period of aortic clamping. The method of treatment including reattachment of intercostal and lumbar arteries (p = 0.2), temporary atriofemoral bypass during aortic occlusion (p = 0.3), and spinal fluid drainage (p = 0.8) were not statistically significant in reducing the incidence of neurologic deficits. Thus cerebrospinal fluid drainage as we used it, was not beneficial in preventing paraplegia. On appropriate statistical analysis we found that the only significant predictor of delayed deficits was postoperative hypotension (p = 0.006).

Chronic neurobrucellosis due to Brucella melitensis.

A 20-year-old male Turkish immigrant to Norway suffering from severe chronic neurobrucellosis with spastic paraplegia and deafness is presented. The diagnosis was established by isolation of Brucella melitensis from cerebrospinal fluid (CSF) culture. Brucella antibody agglutination titers were high in serum and CSF. In spite of intensive, prolonged treatment with a combination of trimethoprim-sulfamethoxazole (TPM-SMZ), rifampicin and doxycycline, the course of the illness was characterized by relapses and severe neurological defects.

Long-term administration of 3'-azido-2',3'-dideoxythymidine to patients with AIDS-related neurological disease.

3'-Azido-2',3'-dideoxythymidine (AZT) has been administered to 7 patients with human immunodeficiency virus-associated neurological disease: 3 with dementia, 2 with peripheral neuropathy, 1 with dementia and peripheral neuropathy, and 1 with T-10 paraplegia. Six of the patients showed improvement in their neurological dysfunction on being administered AZT, as assessed by clinical evaluation, neuropsychological testing, nerve conduction studies, and/or positron emission tomographic scans. Three of these 6 patients showed sustained improvement 5 to 18 months after the initiation of AZT therapy. These results suggest that certain human immunodeficiency virus-associated neurological abnormalities are at least partially reversible following the administration of antiretroviral therapy and provide a rationale for further studies using antiretroviral chemotherapy.

The role of HTLV-I in tropical spastic paraparesis in Jamaica.

We report clinical and laboratory investigations of 47 native-born Jamaican patients with endemic tropical spastic paraparesis and of 1 patient with tropical ataxic neuropathy. Mean age at onset was 40 years, with a female-male preponderance (2.7:1). Neurological features of endemic tropical spastic paraparesis are predominantly those of a spastic paraparesis with variable degrees of proprioceptive and/or superficial sensory impairment. Using enzyme-linked immunoabsorbent assay (ELISA), IgG antibodies to human T-lymphotropic virus type I (HTLV-I) were present in 82% of sera and 77% of cerebrospinal fluids. On Western blot analysis, IgG antibodies detected the p19 and p24 gag-encoded core proteins in both serum and cerebrospinal fluid. Titers were tenfold higher by ELISA in serum than in cerebrospinal fluid, and some oligoclonal bands present in fluid were not seen in serum. Serum-cerebrospinal fluid albumin ratios were normal, and IgG indexes indicated intrathecal IgG synthesis. Histopathological changes showed a chronic inflammatory reaction with mononuclear cell infiltration, perivascular cuffing, and demyelination that was predominant in the lateral columns. In 1 patient, a retrovirus morphologically similar to HTLV-I on electron microscopy was isolated from spinal fluid. Our investigations show that endemic tropical spastic paraparesis in Jamaica is a retrovirus-associated myelopathy and that HTLV-I or an antigenically similar retrovirus is the causal agent.

Tropical spastic paraparesis in Colombia.

A high-incidence focus of tropical spastic paraparesis (TSP) occurs on the South Pacific coast of Colombia. Of 55 patients studied, 52 (94.5%) had IgG antibodies to the human T-cell lymphotropic virus type I (HTLV-I) in serum and/or cerebrospinal fluid. Control groups did not show similar high positivity. Our results suggest that HTLV-I or other antigenically related retroviruses may be the cause of TSP in Colombia. Similar clinical, laboratory, and epidemiological findings have been reported in widely remote geographical regions of the world, with very similar clinical pictures of TSP in all high-incidence regions. The demonstration of IgG antibodies in serum and cerebrospinal fluid of patients with TSP in the Caribbean and Seychelles Islands, southern Japan, and the Ivory Coast indicate that the HTLV-I retrovirus could be the cause of this "tropical" myeloneuropathy.