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Post Reply Close Saving..... Edit Comment Close Premium member Presentation Transcript HypotoniainNeonates and Infants : HypotoniainNeonates and Infants Slide 2: Broad differential diagnosis Common feature of neurologic, metabolic and genetic disorders Frequent indication for Metabolism consultation? Primary indication for Metabolism consultation in 4% of 258 consults (1998-2000) Similar to FTT, liver dysfunction and cardiomyopathy Larger percentage of cases had hypotonia as an additional feature Most hypotonic neonates do not have an underlying Metabolic diagnosis Need comprehensive diagnostic approach Hypotonia Slide 3: Hypotonia and weakness are not the same Tone vs Strength Pathophysiology : Pathophysiology Slide 5: Glucose metabolism via available blood glucose via glycogenolysis FAO oxidative phosphorylation CK-mediated ADP phosphorylation Purine metabolism Mechanisms of ATP productionin muscle Purine nucleotide cycle : Purine nucleotide cycle Myoadenylate deaminase is the myocytic AMP deaminase This pathway produces ATP in intensely exercising muscle Patients with myoadenylate deaminase deficiency present with myalgias and easy fatigue in their 20s or beyond. A few present in childhood ADP x 2 ATP adenylate kinase Slide 7: Complete history and physical exam Historical features Exposures during pregnancy medicines (magnesium) drugs (opiates, ETOH, nicotine, cocaine) infections trauma Fetal movements (tone + power + reflexes) Oligohydramnios Family history Hypotonia evaluation Slide 8: Physical exam Arthrogryposis Joint laxity Congenital hip dislocation Edema Retrognathia Narrow palate Abnormal creases/dimpling “Bell-shaped” thorax Hypotonia evaluation Slide 9: Neonatal posture: 28 wks: arm/leg extension minimal head control 32 wks: arm flexion, leg extension some head control term: arm/leg flexion good head control Signs of hypotonia: Paucity of spontaneous movement May make motor response to arousal “Frog-leg” supine posture Poor head control Poor function on horizontal suspension “Slip through” on vertical suspension “Scarf sign” Neurologic exam Slide 10: finding Hypotonia: predictors of pathology location central peripheral Weakness Encephalopathy Sensory loss Dysmorphic features Seizures Cry Microcephaly Fasciculations Atrophy DTRs + + + + + + + + nl/incr nl/decr high-pitched weak Slide 11: Upper motoneuron Lower motoneuron Neuromuscular junction Myocytes Metabolic pathways Differential Diagnosis Slide 12: Chromosomal Neuronal migration abnormalities Toxic encephalopathies hypermagnesemia opiates hyperammonemia nonketotic hyperglycinemia kernicterus Trauma/IVH Birth asphyxia (HIE) Metabolic/endocrine hypoglycemia peroxisomal disorders hypothyroidism Lysosomal storage disorders Pelizaeus-Merzbacher Primary lactic acidosis Sulfite oxidase deficiency Menke “kinky hair” Other Benign congenital hypotonia Infections sepsis/meningitis/encephalitis TORCH Cerebral Hypoxic ischemic myelopathy Trauma (breech) Tumors Spinal Upper motoneuron diseases Slide 13: Smith’s Recognizable Patterns of Human Malformation 47 syndromes in which hypotonia is a prominent feature Trisomies, Chromosomal deletions, Prader-Willi, Kabuki, Stickler Overgrowth syndromes (Weaver, Sotos, Simpson-Golabi-Behmel) Connective tissue disorders (OI II, EDS I, III, VI, Marfan) Down PWS Zellweger Slide 14: schizencephaly porencephaly lissencephaly toxoplasmosis Slide 15: Lower motoneuron Neuromuscular junction Myocytes Metabolic pathways Anterior horn cell Spinal muscular atrophies 2. Peripheral nerve Hereditary motor and sensory neuropathies (e.g. Charcot-Marie- Tooth) Krabbe Metachromatic leukodystrophy Congenital hypomyelinating polyneuropathy Familial dysautonomia Lower motoneuron diseases SMA 1 (Werdnig - Hoffmann) : SMA 1 (Werdnig - Hoffmann) Dubowitz, V. Muscle Disorders in Childhood, Philadelphia, 1978, WB Saunders Slide 17: Myasthenia gravis Transitory neonatal myasthenia gravis Congenital myasthenia Infantile botulism Neuromuscular junction Diseases of myocytes : Diseases of myocytes Congenital myopathies Central core disease Muscle fiber-type disproportion X-linked myotubular myopathy Nemaline rod myopathy Muscular dystrophies Congenital muscular dystrophy Myotonic dystrophy Nemaline rod myopathy (Gomori trichrome) Nemaline rod myopathy (EM) Metabolic Myopathies : Metabolic Myopathies Substrate for myocyte ATP production depends on: Presence of exercise Intensity of exercise Duration of exercise Rest: FFA Low intensity: Blood glucose, FFA Higher but submaximal intensity: Aerobic glycogen metabolism Maximal intensity: Anaerobic glucose metabolism Mild exercise 0-1 hr: glucose>FFA 1-4 hr: increased FFA uptake >4 hr: FAO is major energy source Metabolic myopathies : Metabolic myopathies Principles 1. In general, exercise intolerance and myoglobinuria in childhood and beyond are hallmarks of presentation. In severe cases, neonatal or infantile hypotonia may result, sometimes in association with multi-system disease. 2. Symptoms can be chronic, episodic or both: Chronic: generalized or proximal weakness, cardiomyopathy, ophthalmoplegia, seizures, developmental delay, FTT Episodic: muscle dysfunction triggered by exercise, infection, cold, fasting, low carbohydrate diet Categories of metabolic myopathies : Categories of metabolic myopathies Glycolysis/glycogenolysis GSD II/acid maltase (Pompe) Phosphorylase system Branching enzyme Debrancher Phosphofructokinase Phosphoglycerate kinase Fatty acid oxidation CTD C/A translocase CPT II VLCAD LCHAD MADD Trifunctional protein SCAD “Mitochondrial” PDH PC Electron transport chain mtDNA mutations MELAS MNGIE mtDNA depletion Evaluating hypotonic neonates : Evaluating hypotonic neonates How do you start working up the patient? Who gets a metabolic workup? General labs Consider sepsis workup Glucose BMP, Ca, Mg CK Toxicology screen Lumbar puncture Head imaging Head ultrasound CT or MRI Other TORCH titers Chromosome, telomere analysis Specific disorders (e.g. PWS probe, SMA, MD molecular) Slide 23: Normal SMA Dubowitz, V. Muscle Disorders in Childhood, Philadelphia, 1978, WB Saunders Evaluating hypotonic neonates EMG, NCS: May help distinguish central vs peripheral hypotonia. May provide specific diagnostic information. Evaluating hypotonic neonates : Evaluating hypotonic neonates Tissues: Muscle: 1. H/E staining 2. PAS staining 3. Gomari staining Fibroblasts: 1. Enzyme assays Other tests: MRSpectroscopy Brain Muscle? EKG, ECHO if metabolic myopathy suspected 4. COX staining 5. EM 6. Enzyme/ETC assays Who needs metabolic workup? : Who needs metabolic workup? Primary goal of consult is to diagnose cause of hypotonia, so workup must be dictated by specifics of case. In a sick, hypotonic neonate, must r/o toxic metabolic encephalopathy as cause of hypotonia (hyperammonemia, metabolic acidosis, etc). These patients are most likely to need metabolic screening labs If clinical picture or screening labs suggest metabolic myopathy, a more tailored approach will be necessary. Sources : Sources http://www.neuro.wustl.edu/neuromuscular.html PEDBASE Miller VS, Delgado M and Iannaccone ST. Neonatal hypotonia. Semin Neurol 13: 73-83 (1993) Parano E and Lovelace RE. Neonatal peripheral hypotonia: clinical and electromyographic characteristics. Child’s Nerv Syst 9: 166-171 (1993) Darras BT and Friedman NR. Metabolic myopathies: a clinical approach; Parts I and II. Pediatr Neurol 22: 87-97 and 171-181 (2000) Tein I. Neonatal metabolic myopathies. Semin Perinat 23: 125-151 (1999) You do not have the permission to view this presentation. In order to view it, please contact the author of the presentation.
Hypotonic Infant samarsen Download Post to : URL : Related Presentations : Share Add to Flag Embed Email Send to Blogs and Networks Add to Channel Uploaded from authorPOINT lite Insert YouTube videos in PowerPont slides with aS Desktop Copy embed code: (To copy code, click on the text box) Embed: URL: Thumbnail: WordPress Embed Customize Embed The presentation is successfully added In Your Favorites. Views: 2235 Category: Education License: All Rights Reserved Like it (3) Dislike it (0) Added: April 13, 2010 This Presentation is Public Favorites: 3 Presentation Description No description available. Comments Posting comment... By: mohammedo (9 month(s) ago) thanks for the prrsentation Saving..... Post Reply Close Saving..... Edit Comment Close By: amalselmi (13 month(s) ago) thank you , it is very usefull, how i can get it please. Saving..... Post Reply Close Saving..... Edit Comment Close By: rizq (14 month(s) ago) can i download it plz Saving..... Post Reply Close Saving..... Edit Comment Close Premium member Presentation Transcript HypotoniainNeonates and Infants : HypotoniainNeonates and Infants Slide 2: Broad differential diagnosis Common feature of neurologic, metabolic and genetic disorders Frequent indication for Metabolism consultation? Primary indication for Metabolism consultation in 4% of 258 consults (1998-2000) Similar to FTT, liver dysfunction and cardiomyopathy Larger percentage of cases had hypotonia as an additional feature Most hypotonic neonates do not have an underlying Metabolic diagnosis Need comprehensive diagnostic approach Hypotonia Slide 3: Hypotonia and weakness are not the same Tone vs Strength Pathophysiology : Pathophysiology Slide 5: Glucose metabolism via available blood glucose via glycogenolysis FAO oxidative phosphorylation CK-mediated ADP phosphorylation Purine metabolism Mechanisms of ATP productionin muscle Purine nucleotide cycle : Purine nucleotide cycle Myoadenylate deaminase is the myocytic AMP deaminase This pathway produces ATP in intensely exercising muscle Patients with myoadenylate deaminase deficiency present with myalgias and easy fatigue in their 20s or beyond. A few present in childhood ADP x 2 ATP adenylate kinase Slide 7: Complete history and physical exam Historical features Exposures during pregnancy medicines (magnesium) drugs (opiates, ETOH, nicotine, cocaine) infections trauma Fetal movements (tone + power + reflexes) Oligohydramnios Family history Hypotonia evaluation Slide 8: Physical exam Arthrogryposis Joint laxity Congenital hip dislocation Edema Retrognathia Narrow palate Abnormal creases/dimpling “Bell-shaped” thorax Hypotonia evaluation Slide 9: Neonatal posture: 28 wks: arm/leg extension minimal head control 32 wks: arm flexion, leg extension some head control term: arm/leg flexion good head control Signs of hypotonia: Paucity of spontaneous movement May make motor response to arousal “Frog-leg” supine posture Poor head control Poor function on horizontal suspension “Slip through” on vertical suspension “Scarf sign” Neurologic exam Slide 10: finding Hypotonia: predictors of pathology location central peripheral Weakness Encephalopathy Sensory loss Dysmorphic features Seizures Cry Microcephaly Fasciculations Atrophy DTRs + + + + + + + + nl/incr nl/decr high-pitched weak Slide 11: Upper motoneuron Lower motoneuron Neuromuscular junction Myocytes Metabolic pathways Differential Diagnosis Slide 12: Chromosomal Neuronal migration abnormalities Toxic encephalopathies hypermagnesemia opiates hyperammonemia nonketotic hyperglycinemia kernicterus Trauma/IVH Birth asphyxia (HIE) Metabolic/endocrine hypoglycemia peroxisomal disorders hypothyroidism Lysosomal storage disorders Pelizaeus-Merzbacher Primary lactic acidosis Sulfite oxidase deficiency Menke “kinky hair” Other Benign congenital hypotonia Infections sepsis/meningitis/encephalitis TORCH Cerebral Hypoxic ischemic myelopathy Trauma (breech) Tumors Spinal Upper motoneuron diseases Slide 13: Smith’s Recognizable Patterns of Human Malformation 47 syndromes in which hypotonia is a prominent feature Trisomies, Chromosomal deletions, Prader-Willi, Kabuki, Stickler Overgrowth syndromes (Weaver, Sotos, Simpson-Golabi-Behmel) Connective tissue disorders (OI II, EDS I, III, VI, Marfan) Down PWS Zellweger Slide 14: schizencephaly porencephaly lissencephaly toxoplasmosis Slide 15: Lower motoneuron Neuromuscular junction Myocytes Metabolic pathways Anterior horn cell Spinal muscular atrophies 2. Peripheral nerve Hereditary motor and sensory neuropathies (e.g. Charcot-Marie- Tooth) Krabbe Metachromatic leukodystrophy Congenital hypomyelinating polyneuropathy Familial dysautonomia Lower motoneuron diseases SMA 1 (Werdnig - Hoffmann) : SMA 1 (Werdnig - Hoffmann) Dubowitz, V. Muscle Disorders in Childhood, Philadelphia, 1978, WB Saunders Slide 17: Myasthenia gravis Transitory neonatal myasthenia gravis Congenital myasthenia Infantile botulism Neuromuscular junction Diseases of myocytes : Diseases of myocytes Congenital myopathies Central core disease Muscle fiber-type disproportion X-linked myotubular myopathy Nemaline rod myopathy Muscular dystrophies Congenital muscular dystrophy Myotonic dystrophy Nemaline rod myopathy (Gomori trichrome) Nemaline rod myopathy (EM) Metabolic Myopathies : Metabolic Myopathies Substrate for myocyte ATP production depends on: Presence of exercise Intensity of exercise Duration of exercise Rest: FFA Low intensity: Blood glucose, FFA Higher but submaximal intensity: Aerobic glycogen metabolism Maximal intensity: Anaerobic glucose metabolism Mild exercise 0-1 hr: glucose>FFA 1-4 hr: increased FFA uptake >4 hr: FAO is major energy source Metabolic myopathies : Metabolic myopathies Principles 1. In general, exercise intolerance and myoglobinuria in childhood and beyond are hallmarks of presentation. In severe cases, neonatal or infantile hypotonia may result, sometimes in association with multi-system disease. 2. Symptoms can be chronic, episodic or both: Chronic: generalized or proximal weakness, cardiomyopathy, ophthalmoplegia, seizures, developmental delay, FTT Episodic: muscle dysfunction triggered by exercise, infection, cold, fasting, low carbohydrate diet Categories of metabolic myopathies : Categories of metabolic myopathies Glycolysis/glycogenolysis GSD II/acid maltase (Pompe) Phosphorylase system Branching enzyme Debrancher Phosphofructokinase Phosphoglycerate kinase Fatty acid oxidation CTD C/A translocase CPT II VLCAD LCHAD MADD Trifunctional protein SCAD “Mitochondrial” PDH PC Electron transport chain mtDNA mutations MELAS MNGIE mtDNA depletion Evaluating hypotonic neonates : Evaluating hypotonic neonates How do you start working up the patient? Who gets a metabolic workup? General labs Consider sepsis workup Glucose BMP, Ca, Mg CK Toxicology screen Lumbar puncture Head imaging Head ultrasound CT or MRI Other TORCH titers Chromosome, telomere analysis Specific disorders (e.g. PWS probe, SMA, MD molecular) Slide 23: Normal SMA Dubowitz, V. Muscle Disorders in Childhood, Philadelphia, 1978, WB Saunders Evaluating hypotonic neonates EMG, NCS: May help distinguish central vs peripheral hypotonia. May provide specific diagnostic information. Evaluating hypotonic neonates : Evaluating hypotonic neonates Tissues: Muscle: 1. H/E staining 2. PAS staining 3. Gomari staining Fibroblasts: 1. Enzyme assays Other tests: MRSpectroscopy Brain Muscle? EKG, ECHO if metabolic myopathy suspected 4. COX staining 5. EM 6. Enzyme/ETC assays Who needs metabolic workup? : Who needs metabolic workup? Primary goal of consult is to diagnose cause of hypotonia, so workup must be dictated by specifics of case. In a sick, hypotonic neonate, must r/o toxic metabolic encephalopathy as cause of hypotonia (hyperammonemia, metabolic acidosis, etc). These patients are most likely to need metabolic screening labs If clinical picture or screening labs suggest metabolic myopathy, a more tailored approach will be necessary. Sources : Sources http://www.neuro.wustl.edu/neuromuscular.html PEDBASE Miller VS, Delgado M and Iannaccone ST. Neonatal hypotonia. Semin Neurol 13: 73-83 (1993) Parano E and Lovelace RE. Neonatal peripheral hypotonia: clinical and electromyographic characteristics. Child’s Nerv Syst 9: 166-171 (1993) Darras BT and Friedman NR. Metabolic myopathies: a clinical approach; Parts I and II. Pediatr Neurol 22: 87-97 and 171-181 (2000) Tein I. Neonatal metabolic myopathies. Semin Perinat 23: 125-151 (1999)