Mutational study in the PDHA1 gene of 40 patients suspected of pyruvate dehydrogenase complex deficiency.

We screened for PDHA1 mutations in 40 patients with biochemically demonstrated PDHc deficiency or strong clinical suspicion, and found changes with probable pathological significance in 20. Five patients presented new mutations: p.A169V, c.932_938del, c.1143_1144 ins24, c.1146_1159dup and c.510-30G> A, this latter is a new undescribed cause of exon 6 skipping. Another four mutations have been found, and previously reported, in our patients: p.H113D, p.P172L, p.Y243del and p.Y369Q. Eleven patients presented seven known mutations: p.R127Q, p.I166I, p.A198T, p.R263G, p.R302C, p.R378C and c.1142_1145dup. The latter three were found in more than one unrelated patient: p.R302C was detected in a heterozygous girl and a mosaic male, p.R378C in two males and finally, c.1142_1145dup in three females; only one in 20 mothers was found to be a carrier (p.R263G). Apart from those 20 patients, the only alteration detected in one girl with clear PDHc and PDH-E1 deficiency was the silent change c.396A> C (p.R132R), and other eight PDHc deficient patients carry combinations of known infrequent polymorphisms that are overrepresented among our 20 unsolved patients. The importance of these changes on PDH activity is unclear. Investigations in the other PDHc genes are in course in order to elucidate the genetic defect in the unresolved patients.

PDH E1ß deficiency with novel mutations in two patients with Leigh syndrome.

Most cases of pyruvate dehydrogenase complex (PDHc) deficiency are attributable to mutations in the PDHA1 gene which encodes the E(1)α subunit, with few cases of mutations in the genes for E(3), E3BP (E(3) binding protein), E(2) and E(1)-phosphatase being reported. Only seven patients with deficiency of the E(1)ß subunit have been described, with mutations in the PDHB gene in six of them. Clinically they presented with a non-specific encephalomyopathy. We report two patients with new mutations in PDHB and Leigh syndrome. Patient 1 was a boy with neonatal onset of hyperlactataemia, corpus callosum hypoplasia and a convulsive encephalopathy. After neurological deterioration, he died at age 5 months. Autopsy revealed the characteristic features of Leigh syndrome. Patient 2, also a boy, presented a milder clinical course. First symptoms were noticed at age 16 months with muscular hypotonia, lactic acidosis and recurrent episodes of somnolence and transient tetraparesis. MRI revealed bilateral signal hyperintensities in the globus pallidus, midbrain and crura cerebri. PDHc and E(1) activities were deficient in fibroblasts in patient 1; in patient 2 PDHc deficiency was found in skeletal muscle. Mutations in PDHA1 were excluded. Sequencing of PDHB revealed a homozygous point mutation (c.302T>C), causing a predicted amino acid change (p.M101T) in patient 1. Patient 2 is compound heterozygote for mutations c.301A>G (p.M101V) and c.313G>A (p.R105Q). All three mutations appear to destabilize the E(1) enzyme with a decrease of both E(1)α and E(1)ß subunits in immunoblot analysis. To our knowledge, these patients with novel PDHB mutations are the first reported with Leigh syndrome.

[Patient satisfaction with spinal cord stimulation for failed back surgery syndrome]. / Satisfacción del paciente con síndrome de dolor de raquis postquirúrgico portador de un sistema de neuroestimulación medular.

INTRODUCTION: The incidence of failed back surgery syndrome is about 40%. We studied the efficacy of and patient satisfaction with use of a spinal cord stimulator to treat this syndrome. MATERIAL AND METHODS: A period of 72 months of experience with implanted spinal cord stimulators was analyzed in this observational, descriptive study of patients who were included retrospectively. Patients met criteria for failed back surgery syndrome according to the taxonomy of the International Association for the Study of Pain. A chi2 test was used to compare qualitative variables. Results for quantitative variables were compared by analysis of variance. Statistical significance was set at P < 0.05. RESULTS: Thirty-four patients were studied. Both lumbar back and radicular pain assessed on a visual analog scale (VAS) decreased significantly from the mean overall score of 6. As time passed, fewer patients felt the system met their expectations. More patients said the system met their expectations in the first months after implantation (73.5%) than at a later interview (55.9%). Seventeen complications were reported, the most common being mechanical difficulties with the implanted stimulator. None of the complications were serious. Use of additional medication to control pain decreased in 38.2% of the cases. A total of 73.5% of the patients considered the implanted stimulator to be beneficial and 67.6% would have a spinal cord stimulator implanted again. CONCLUSIONS: Spinal cord stimulation improves lumbar back pain in patients with failed back surgery syndrome and reduces the amount of additional medication taken to control pain. It is important for patients to adjust their expectations about the implanted stimulator.

[Ketamine for subarachnoid anesthesia during hypovolemia: preliminary study in pigs]. / Utilización de ketamina para anestesia subaracnoidea durante hipovolemia. Estudio experimental preliminar en cerdos.

OBJECTIVES: To assess whether subarachnoid ketamine has fewer hemodynamic effects than lidocaine in normal and hypovolemic pigs and to determine whether or not the effects of ketamine are dose-dependent. METHODS: Thirty pigs were randomly allocated to receive subarachnoid administration of lidocaine 2 mg x kg(-1), ketamine 1 mg x kg(-1) or ketamine 2 mg x kg(-1), in a situation of either normal or reduced blood volume. The pigs were assigned to six groups: group L2 (2% lidocaine 2 mg x kg(-1), normovolemia), group L2H (2% lidocaine 2 mg x kg(-1), hypovolemia), group K1 (ketamine 1 mg x kg(-1), normovolemia), group K1H (ketamine 1 mg x kg(-1), hypovolemia), group K2 (ketamine 2 mg.kg(-', normovolemia), and group K2H (ketamine 2 mg x kg(-1), hypovolemia). To induce hypovolemia 30% of the calculated blood volume was withdrawn from each pig. The subarachnoid space was catheterized, and invasive measurements of hemodynamic variables (derived from arterial, central venous and pulmonary artery catheter monitoring) were obtained. Variables were recorded at baseline and 5 and 15 min after drug injection in the normovolemic groups, and at baseline after inducing hypovolemia and 5 and 15 min after drug injection in the hypovolemic groups. RESULTS: In the normovolemic pigs no significant differences were detected between groups. In hypovolemic pigs differences were observed in heart rate and arterial pressure between the ketamine 1 mg x kg(-1) and lidocaine 2 mg x kg(-1) groups (P < 0.05). The decreases in heart rate and arterial pressure were less marked in the ketamine group. Mixed venous oxygen saturation and cardiac index deteriorated to a lesser degree in both ketamine groups than in the lidocaine groups (P < 0.05). CONCLUSIONS: Racemic ketamine administered by subarachnoid injection in hypovolemic pigs produces less deterioration in hemodynamic variables than does lidocaine. Hemodynamic changes caused by ketamine were not dose-dependent. These findings may be of interest, given the increased use of ketamine in neuroaxial anesthesia and analgesia and perhaps the possible use of neuroaxial ketamine in hypovolemic patients.

[Spinal and cerebral hematoma following diagnostic lumbar puncture with fatal course]. / Hematoma espinal y cerebral postpunción lumbar diagnóstica con evolución letal.

A 64-year-old man suspected of having neurosyphillis suffered subarachnoid spinal and cerebral ventricular hemorrhage after a diagnostic lumbar puncture. The main risk factor was trauma occurring during a difficult puncture. Both the diagnosis and the subsequent laminectomy were delayed. Blood migrated to both lateral ventricles, complicating the clinical course, which ended in death. The need for rapid diagnosis and treatment in such cases is revealed by both images and clinical course. A pathophysiologic explanation for these hemorrhagic events is provided.

Management of progressive pain in a patient with intramedullary chordoma of the spine.

OBJECTIVES: The case here presented adequately reflects the difficulties involved in the treatment of pain in patients where the neuropathic component of pain predominates, and shows the different therapeutic steps that may be taken-from surgery and radiotherapy, to the administration of different drugs via the spinal route, to, finally, the presently little-used option of a direct intraventricular access. CONCLUSIONS: Spinal tumors are infrequent, but pose great difficulties for the management and control of the pain they cause. The utility of the spinal route as an early approach for the provision of adequate analgesia seems clear. However, it also appears to lose efficacy with time, and dose incrementing and/or the addition of drugs that enhance the analgesic action of morphine are not always effective. In such selected cases, the intraventricular route may constitute a useful alternative, allowing improved symptoms control with lower morphine doses, and the use of the system previously implanted for intrathecal spinal infusion.

Repeated subarachnoid catheter displacement as a complication of spinal infusion using an internal infusion pump.

OBJECTIVE: To present and analyze the case of a woman receiving chronic spinal opioid therapy using an implanted infusion pump who experienced repeated displacement of the subarachnoid catheter despite the use of standard techniques for anchoring the catheter. The solution devised to avoid the problem is described. CASE REPORT: A 53-year-old woman was diagnosed with transverse myelitis 10 years earlier and she developed T7-T10 spinal cord atrophy, and pain below the T7 segment. After unsuccessful noninvasive pharmacological treatment, a spinal opioid infusion protocol was begun. On 3 occasions during the course of therapy, despite the use of standard measures for anchoring the system, catheter displacement into the subcutaneous pouch of the pump occurred. After the last such episode, a specially designed technique was used, anchoring the catheter by means of a silicone piece, and the injection of 2.5 mL of fibrin glue in the epidural space. CONCLUSIONS: The application of fibrin glue (Tissucol; Immuno AG, Vienna, Austria) may be considered as an adjuvant for the fixation of subarachnoid catheters used for intraspinal infusions.

Epidural and subarachnoidal pneumocephalus after epidural technique.

Iatrogenic pneumocephalus is an uncommon complication observed after using the 'loss-of-resistance' technique with an air filled syringe. We report and review two cases of pneumocephalus: one subarachnoid and the other epidural.

Subarachnoid ketamine in swine--pathological findings after repeated doses: acute toxicity study.

BACKGROUND AND OBJECTIVES: The purpose of this study was to investigate whether 5% ketamine with and without preservative, administered intrathecally to swine, produced a clinical anesthetic effect and caused direct subacute neurotoxicity. METHODS: Twenty pigs were used. Under general anesthesia, a subarachnoid catheter was placed at L5-L6 or L6-S1 spinal interspace. Five animals were used for initial clinical evaluation of the anesthetic effects of subarachnoid ketamine (12.5 and 25.0, and 500 mg). Two animals were excluded because of bloody taps, two served as controls (catheterization without drug administration), four received ketamine racemate (25.0 mg/d), four received ketamine racemate preservative free (25.0 mg/d), and three received benzethonium chloride, the ketamine excipient (0.05 mg/d). All drugs were administered for 7 days. The catheters were withdrawn at the end of the treatment period. After 35 days, the pigs were euthanized and the spinal cord removed and preserved for histopathologic study with hematoxilyn-eosin and luxol-fast blue myelin staining. Histopathologic effects were defined as absent/minimal, mild, or severe by a pathologist, unaware of group allocation, by evaluating the presence and intensity of peripheral and/or central chromatolysis, spongiosis, neuronal loss, perivascular neuroglia, neuronolysis, and myelin degeneration. RESULTS: All doses of ketamine produced immediate cutaneous anesthesia and motor block; benzethonium chloride did not. Histopathologic examination showed no neurotoxic effect of ketamine without preservative; ketamine with preservative showed a discrete neurotoxic effect, and the preservative alone produced a moderate neurotoxic effect. CONCLUSIONS: Clinically, in swine, subarachnoid ketamine without preservative is a safe and effective anesthetic and did not show significant neurotoxic effects. However, ketamine with preservative produces minimal changes, and benzethonium chloride alone produces moderate neurotoxic effects.

[Cardiocirculatory effects of intravenous anesthetic induction in an experimental model of acute hypovolemia]. / Efectos cardiocirculatorios de la inducción anestésica intravenosa en un modelo experimental de hipovolemia aguda.

OBJECTIVE: To evaluate the cardiovascular effects of ketamine, midazolam, thiopentone and propofol in acutely hypovolemic pigs and to determine whether the association of ketamine and midazolam offers any advantage. PATIENTS AND METHODS: Twenty-two Landrace-Large-White pigs. After monitoring was begun, acute hypovolemia was induced by means of rapid exsanguination of 30% of calculated volume. Hemodynamic variables were measured: a) at baseline; b) after exsanguination; c) 2 min after anesthetic induction; d) 10 min after anesthetic induction, and e) after reinfusion of the exsanguinated volume. RESULTS: All pressures, cardiac output, cardiac index, and mixed venous oxygen saturation fell significantly with the induction of hypovolemia. Heart rate, systemic vascular resistances and arteriovenous oxygen differential increased. Ten min after anesthetic induction, heart rate in the midazolam group was significantly lower than in the ketamine-midazolam group. Arterial pressures decreased significantly after anesthetic induction with all drugs. The decrease in systolic arterial pressure was smaller in thiopenthal-anesthetized pigs than in pigs receiving either midazolam or propofol at the 10 min recording. The decrease in mean arterial and diastolic pressure after 10 min was smaller with thiopental than with any other drug. The decrease in mean arterial pressure was less in the thiopental and ketamine-midazolam groups than in the others after reinfusion. Diastolic arterial pressure at 10 min and after reinfusion had decreased less in the thiopental and ketamine-midazolam groups than in the propofol group. After anesthetic induction, the post-hypovolemic figures for cardiac output and cardiac index held steady or changes were slightly accentuated, with no statistically significant differences among the groups. CONCLUSIONS: The intravenous anesthetics evaluated were detrimental to cardiovascular function in acute hypovolemic pigs. Low-dose thiopental and ketamine plus midazolam may be the anesthetics of choice in this setting. Propofol caused the greatest degree of hemodynamic instability.