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Multiple disease categories screening analysis (MULTISCAN) by tandem mass spectrometry in urine, plasma and dried blood spots (DBS)
Swiss Society of Clinical Neurophysiology / Clinical Neurophysiology 118 (2007) e1–e7
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Multiple disease categories screening analysis (MULTISCAN) by tandem mass spectrometry in urine, plasma and dried blood spots (DBS)—H. Korall (Children’s Hospital, Reutlingen, Germany)
Intraoperative MEP-monitoring is useful in spinal cord surgery: it is simple, provides fast reliable information with excellent clinical correlation and a pattern of change indicating reversible injury.
Introduction: Clinical symptoms of inborn errors of metabolism (IEOM) are partially unspecific. Using tandem mass spectrometry (TMS) we developed multiple disease categories screening analysis (MULTISCAN), an advanced selective screening method in urine and plasma for detecting IEOM. Method: Urine metabolites were separated by a column and quantified by TMS. We show new applications with TMS screening for common and rare metabolic diseases. Plasma metabolites like homocysteine, phytanic acid and very long-chain-fatty acids (VLCFA) were detected, too. In most cases quantification of pathognomic metabolites is based on stable isotopes dilution technique as internal standards. Result: In just a few minutes run all relevant aminoacids and additional pathognomic metabolites are detected. Key metabolites, e.g. pipecolic acid for a urine preselection in peroxisomal disorders, guanidinoacetate and creatine for the diagnosis of guanidinoacetate methyl transferase deficiency (GAMT), globotriaosylceramides (GL-3) in Fabry disease, purines and pyrimidines are screened, too. Peroxisomal disorders may be confirmed by quantification of phytanic acid and VLCFA in plasma. Furthermore by this applications we found new approaches in quick, reliable and adequate therapy control of IOEM. Summary: MULTISCAN is a rapid, sensitive and reliable diagnostic tool for an effective, selective screening and therapy monitoring in IEOM.
doi:10.1016/j.clinph.2006.06.729
doi:10.1016/j.clinph.2006.06.728
Horizontal gaze palsy with progressive scoliosis (HGPPS)— J. Lu¨tschg, P. Weber (Department of Neuropaediatry, University Hospital Bruderholz, Basle, Switzerland) HGPPS is due to a mutation in the ROBO3 gene, which regulates the midline crossing of axons during the early brain development. In this paper a 13 years old boy is presented. His first symptoms were jerking head movements. A horizontal gaze palsy including convergence weakness, normal vertical eye movements, a scoliosis and a gait ataxia were found in the neurological examination. The MRI showed a hypoplastic pons with a midline cleft. A defect in the ROBO3 gene was confirmed. Somatosensory evoked potentials (stimulation of the median nerve at the wrist) were elicitable only ipsilaterally and motor evoked potentials were ipsilaterally more pronounced than contralaterally. In the near infrared spectroscopy (NIRS) an increase of HbO2 is seen bilaterally after unilateral hand movements. These neurophysiological results confirm the lack of crossing of motor and sensory tracts. However in more complex unilateral tasks both hemispheres are activated doi:10.1016/j.clinph.2006.06.730
Intraoperative motor evoked potential monitoring during surgery for intramedullary spinal cord tumors—K.F. Kothbauer (Department of Neurosurgery, Cantonal Hospital, Lucerne, Switzerland)
Improvement of dystonia and self-mutilating behavior by motor and limbic GPi stimulation in Lesch-Nyhan syndrome (LNS)—C. Pollo, E. Roulet, F. Vingehoets, E. Pralong, D. Debatisse, J. Bloch, J.G. Villemure, P. Coubes (UNN-NS, University Hospital, Lausanne, Switzerland)
For intraoperative monitoring to be useful three conditions must be met: 1. recording must be simple and fast, 2. the data must reflect the clinical ‘‘reality’’, and 3. changes in recordings must indicate a damage as long as it is reversible. Motor potentials are evoked with transcranial electric stimulation of the motor cortex: with a ‘‘single pulse’’ technique a ‘‘Dwave’’ in the corticospinal tracts is evoked and recorded over the spinal cord. A ‘‘multi-pulse’’ technique allows recording of muscle responses. Experience from over 300 intramedullary procedures is the basis for this assessment. Monitoring with motor evoked potentials (MEPs) is feasible in the operating room. Preparations require little time during anesthesia induction. No longterm or significant complications have occurred. D-wave amplitudes and the presence or absence of muscle MEPs correlate with pre-and postoperative neurological status: there are 10% of false-positive recordings (MEPs indicating a deficit which is not seen), and no false-negatives (MEPs missing a deficit). Loss of muscle MEPs combined with preservation of Dwave is the neurophysiological correlate of a transient motor deficit and a concept of reversibility: neurophysiological ‘‘warning’’ to the surgeon before irreversible damage has occurred.
Background and purpose: LNS is a rare X-linked hereditary disorder caused by a deficiency of hypoxanthine-guanine phosphoribosyltransferase and is characterized by self-mutilation and movement disorders such as spasticity and dystonia. GPi stimulation has been reported to improve dystonia but its effectiveness on the self-mutilating behavior remains unclear. We present 4 cases of LNS who were stimulated in the ‘‘motor’’ and ‘‘limbic’’ portion of the GPi and in which an improvement in both symptoms was observed. Methods: A stereotactic 3D T1-weighted MR acquisition was performed under general anesthesia. The limbic and motor pallidal targets were determined visually. Postoperative MRI under general anesthesia was performed to verify the electrode position. Stimulators were implanted in the subcostal region bilaterally. Monopolar stimulation (PW = 450 ms, rate = 130 Hz) was performed on both distal contacts of each electrode. Results: Improvement of the self-mutilating behavior and dystonic symptoms (hemiballic movements and opistotonos) were observed (BFMDRS improvement 33–46%). No stimulation-induced side effects were noticed.
e3
Multiple disease categories screening analysis (MULTISCAN) by tandem mass spectrometry in urine, plasma and dried blood spots (DBS)—H. Korall (Children’s Hospital, Reutlingen, Germany)
Intraoperative MEP-monitoring is useful in spinal cord surgery: it is simple, provides fast reliable information with excellent clinical correlation and a pattern of change indicating reversible injury.
Introduction: Clinical symptoms of inborn errors of metabolism (IEOM) are partially unspecific. Using tandem mass spectrometry (TMS) we developed multiple disease categories screening analysis (MULTISCAN), an advanced selective screening method in urine and plasma for detecting IEOM. Method: Urine metabolites were separated by a column and quantified by TMS. We show new applications with TMS screening for common and rare metabolic diseases. Plasma metabolites like homocysteine, phytanic acid and very long-chain-fatty acids (VLCFA) were detected, too. In most cases quantification of pathognomic metabolites is based on stable isotopes dilution technique as internal standards. Result: In just a few minutes run all relevant aminoacids and additional pathognomic metabolites are detected. Key metabolites, e.g. pipecolic acid for a urine preselection in peroxisomal disorders, guanidinoacetate and creatine for the diagnosis of guanidinoacetate methyl transferase deficiency (GAMT), globotriaosylceramides (GL-3) in Fabry disease, purines and pyrimidines are screened, too. Peroxisomal disorders may be confirmed by quantification of phytanic acid and VLCFA in plasma. Furthermore by this applications we found new approaches in quick, reliable and adequate therapy control of IOEM. Summary: MULTISCAN is a rapid, sensitive and reliable diagnostic tool for an effective, selective screening and therapy monitoring in IEOM.
doi:10.1016/j.clinph.2006.06.729
doi:10.1016/j.clinph.2006.06.728
Horizontal gaze palsy with progressive scoliosis (HGPPS)— J. Lu¨tschg, P. Weber (Department of Neuropaediatry, University Hospital Bruderholz, Basle, Switzerland) HGPPS is due to a mutation in the ROBO3 gene, which regulates the midline crossing of axons during the early brain development. In this paper a 13 years old boy is presented. His first symptoms were jerking head movements. A horizontal gaze palsy including convergence weakness, normal vertical eye movements, a scoliosis and a gait ataxia were found in the neurological examination. The MRI showed a hypoplastic pons with a midline cleft. A defect in the ROBO3 gene was confirmed. Somatosensory evoked potentials (stimulation of the median nerve at the wrist) were elicitable only ipsilaterally and motor evoked potentials were ipsilaterally more pronounced than contralaterally. In the near infrared spectroscopy (NIRS) an increase of HbO2 is seen bilaterally after unilateral hand movements. These neurophysiological results confirm the lack of crossing of motor and sensory tracts. However in more complex unilateral tasks both hemispheres are activated doi:10.1016/j.clinph.2006.06.730
Intraoperative motor evoked potential monitoring during surgery for intramedullary spinal cord tumors—K.F. Kothbauer (Department of Neurosurgery, Cantonal Hospital, Lucerne, Switzerland)
Improvement of dystonia and self-mutilating behavior by motor and limbic GPi stimulation in Lesch-Nyhan syndrome (LNS)—C. Pollo, E. Roulet, F. Vingehoets, E. Pralong, D. Debatisse, J. Bloch, J.G. Villemure, P. Coubes (UNN-NS, University Hospital, Lausanne, Switzerland)
For intraoperative monitoring to be useful three conditions must be met: 1. recording must be simple and fast, 2. the data must reflect the clinical ‘‘reality’’, and 3. changes in recordings must indicate a damage as long as it is reversible. Motor potentials are evoked with transcranial electric stimulation of the motor cortex: with a ‘‘single pulse’’ technique a ‘‘Dwave’’ in the corticospinal tracts is evoked and recorded over the spinal cord. A ‘‘multi-pulse’’ technique allows recording of muscle responses. Experience from over 300 intramedullary procedures is the basis for this assessment. Monitoring with motor evoked potentials (MEPs) is feasible in the operating room. Preparations require little time during anesthesia induction. No longterm or significant complications have occurred. D-wave amplitudes and the presence or absence of muscle MEPs correlate with pre-and postoperative neurological status: there are 10% of false-positive recordings (MEPs indicating a deficit which is not seen), and no false-negatives (MEPs missing a deficit). Loss of muscle MEPs combined with preservation of Dwave is the neurophysiological correlate of a transient motor deficit and a concept of reversibility: neurophysiological ‘‘warning’’ to the surgeon before irreversible damage has occurred.
Background and purpose: LNS is a rare X-linked hereditary disorder caused by a deficiency of hypoxanthine-guanine phosphoribosyltransferase and is characterized by self-mutilation and movement disorders such as spasticity and dystonia. GPi stimulation has been reported to improve dystonia but its effectiveness on the self-mutilating behavior remains unclear. We present 4 cases of LNS who were stimulated in the ‘‘motor’’ and ‘‘limbic’’ portion of the GPi and in which an improvement in both symptoms was observed. Methods: A stereotactic 3D T1-weighted MR acquisition was performed under general anesthesia. The limbic and motor pallidal targets were determined visually. Postoperative MRI under general anesthesia was performed to verify the electrode position. Stimulators were implanted in the subcostal region bilaterally. Monopolar stimulation (PW = 450 ms, rate = 130 Hz) was performed on both distal contacts of each electrode. Results: Improvement of the self-mutilating behavior and dystonic symptoms (hemiballic movements and opistotonos) were observed (BFMDRS improvement 33–46%). No stimulation-induced side effects were noticed.