Diagnosis of Spinal Muscular Atrophy
Spinal Muscular Atrophy Diagnosis: Book Excerpts
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MUSCULAR ATROPHY:
Ask the Following Questions:
(Algorithmic Diagnosis of Symptoms and Signs)
- Is it focal or diffuse? Focal muscular atrophy would suggest poliomyelitis, early spinal muscular atrophy, peripheral vascular disease, and sympathetic dystrophy. However, occasionally it is an indication of an early spinal cord tumor, herniated disk, or peroneal muscular atrophy. It can also be a sign of an entrapment syndrome of one of the peripheral nerves. Focal muscular atrophy with hyperactive reflexes suggests amyotrophic lateral sclerosis, multiple sclerosis, spinal cord tumors, or syringomyelia.
- Are the reflexes hypoactive or hyperactive? Muscular atrophy with hypoactive reflexes suggests peripheral neuropathy, poliomyelitis, spinal muscular atrophy, myasthenia gravis, peripheral vascular disease, sympathetic dystrophy, herniated disk, early spinal cord tumor, and peroneal muscular atrophy. Muscular atrophy with hyperactive reflexes suggests multiple sclerosis, spinal cord tumors, syringomyelia, and amyotrophic lateral sclerosis.
- Are there associated sensory changes? The finding of muscular atrophy with sensory changes suggests a peripheral neuropathy, Guillain-Barré syndrome, Friedreich's ataxia, multiple sclerosis, transverse myelitis, a herniated disk, spinal cord tumor, and peroneal muscular atrophy. It may also suggest syringomyelia.
- Are the reflexes normal? The presence of normal reflexes suggests anorexia nervosa, tuberculosis, metastatic malignancy, and hyperthyroidism.
DIAGNOSTIC WORKUP
The basic workup includes a CBC, sedimentation rate, urinalysis, chemistry panel, ANA titer, serum protein electrophoresis, and VDRL test. Additional muscle enzymes may be ordered such as serum aldolase and CPK. A 24-hr urine collection for creatinine and creatine may be done.
At this point, it is best to consult a neurologist. He will probably order nerve conduction velocity studies and EMGs of the involved extremities. He also will be best qualified to determine the need for CT scans or MRIs of the brain or spine, as well as the particular study to order in each individual case. At times, spinal fluid analysis and muscle biopsies may be necessary to solve the problem. Also, a Tensilon test or acetylcholine receptor antibody titer may be ordered in suspected myasthenia gravis.
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Source: Algorithmic Diagnosis of Symptoms and Signs, 2003
MUSCULAR ATROPHY:
Approach to the Diagnosis
(Differential Diagnosis in Primary Care)
Focal atrophy of a muscle often means a damaged peripheral nerve or root. If there are visible fasciculations, a lesion of the spinal cord or root is most likely. Electromyography will determine which portion of the nerve is affected. It will also be helpful in diagnosing muscle disease. Muscle biopsy is valuable to rule out trichinosis, dermatomyositis, or muscular dystrophy. If there are fasciculations, a spine x-ray, spinal tap, and myelography or MRI may be necessary to establish the diagnosis. Sedimentation rate, CRP, RA titer, ANA, and tuberculin tests may be necessary.
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Source: Differential Diagnosis in Primary Care, 2007
Alteration in Consciousness:
Clinical Features and Diagnosis
(The Diagnostic Approach to Symptoms and Signs in Pediatrics)
Head Trauma
Concussion
Definedas transient loss of neurologic function that usually involves lossof consciousness (seconds or minutes) after head trauma. Postconcussionsyndrome consisting of nausea, vomiting, headache, and lassitudemay last hours or days.Diagnosis is made by the history, absenceof focal neurologic findings on physical exam, and normal brainimaging. Brain Contusion
Definedas area of microscopic disruption of cellular architecture of brain.May occur directly below area of injuryor as contrecoup lesion from acceleration-deceleration injury.Some contusions increase in size infirst few days after injury and produce mass effect with contralateralshift of midline structures.Small contusions usually resolve spontaneously.CT or MRI is diagnostic. Shearing Injury
Axonal injuryof white matter occurs.Clinical spectrum varies from mildconcussion to coma.CT is diagnostic, but MRI yields morespecific information, especially in individuals with unexplainedneurologic deficits or persistent loss of consciousness. Cerebral Edema
Diffusecerebral edema is more common than focal lesion after head trauma.Persistent loss of consciousness isusual clinical manifestation of severe cerebral edema.CT findings of loss of gray-white interfacemay not be visible until 12–24 hrs after brain injury. Intracranial Hemorrhage
Intraparenchymal Hemorrhage
Usuallyoccurs from direct blow to head or a penetrating injury.Clinical manifestations include headache,vomiting, seizures, and alteration in consciousness.CT is diagnostic. Subdural Hematoma
Definedas collection of blood beneath dura.Produced by tearing of cortical bridgingveins between dura and arachnoid.Whether alteration of consciousnessoccurs depends on how severe injury is and size of hematoma.Shaking injury in infants <1yr also may produce subdural hematoma, as well as seizures, bulgingfontanelle, retinal hemorrhages, and apnea.CT is diagnostic. Epidural Hematoma
Definedas collection of blood between dura and skull that occurs from bleedingfrom cerebral arteries or veins.May be associated with overlying skullfracture.Loss of consciousness may occur attime of injury or in 1–2 days, when hematoma enlarges. Vomiting,headache, and seizures also may occur.CT is diagnostic. Infection/Inflammation
Bacterial Meningitis
Most commonintracranial infection that produces alteration in consciousness.Group B Streptococcus and gram-negativeenteric bacteria are most common pathogens in neonates, whereasS. pneumoniae and N. meningitidis are most common in infants andchildren. H. influenzae type b has become much less common sincedevelopment of H. influenzae vaccine.Clinical findings include fever, irritability,headache, vomiting, stiff neck, bulging fontanelle, and seizures.Kernig and Brudzinski signs indicate meningeal irritation, but meningealsigns may not be present in infants.Analysis of CSF reveals pleocytosisincluding many polymorphonuclear leukocytes, increased protein,and usually decreased glucose. Gram stain of spinal fluid is oftenpositive, and positive culture is diagnostic.Detection of polysaccharide antigens(S. pneumoniae, N. meningitidis, group B Streptococcus) in CSF bylatex agglutination is also diagnostic. Encephalitis
Definedas inflammatory process that involves brain. Pathogens include enteroviruses,measles virus, mumps virus, rabies virus, herpes simplex virus,varicella-zoster virus, Epstein-Barr virus, cytomegalovirus, arboviruses,M. pneumoniae, and rickettsiae.Clinical findings include fever, headache,vomiting, ataxia, seizures, and alteration in consciousness.CSF analysis usually reveals increasedcell count with primarily mononuclear cells, normal or mildly increasedprotein level, and normal glucose level.MRI may demonstrate inflammation ofcerebral cortex, gray-white matter junction, or basal ganglia.Diagnostic tests include appropriatecultures, polymerase chain reaction, and serologic methods.Postinfectious encephalitis is autoimmuneprocess that usually follows preceding viral infection within 1–2wks. Clinical findings are similar to those that occur with infectiousencephalitis. MRI often shows demyelination in multiple areas ofbrain. Septicemia
Ill childrenmay have alteration in consciousness.Most common pathogens in neonates aregroup B Streptococcus and E. coli, whereas S. pneumoniae, N. meningitidis,group A Streptococcus, and S. aureus are most common in infantsand children.Positive blood culture is diagnostic. Focal Infection
Brain Abscess
Definedas localized collection of pus in cerebral hemispheres or cerebellum.Predisposing factors are meningitis,sinusitis, chronic otitis media, mastoiditis, bacterial pneumonia,dental infection, endocarditis, congenital heart disease, and penetratinghead trauma.Most common pathogens include Streptococcusspecies, Staphylococcus species, H. influenzae, N. meningitidis,Enterobacteriaceae, and anaerobes. Fungi and mycobacteria also maycause brain abscess.Location of abscess and presence ofmass effect determine presentation.Clinical manifestations include fever,headache, vomiting, seizures, ataxia, hemiparesis, visual fielddefects, papilledema, and alteration in consciousness.CT or MRI is usually diagnostic.Pathogens may be cultured from bloodor CSF in about 10% of cases. Yield of positive CSF culturesis higher in individuals with coexisting meningitis or rupture ofabscess into subarachnoid space. Lumbar puncture should not be performeduntil increased intracranial pressure has been excluded by CT orMRI.Sometimes specific pathogen may beidentified by culturing abscess contents obtained from CT-guidedaspiration or surgical excision of abscess. These procedures mayneed to be performed when patients do not meet criteria for medicaltreatment alone. Epidural Abscess
Occurs inepidural space between dura and skull.Risk factors include sinusitis, otitismedia, orbital cellulitis, meningitis, and osteomyelitis.Most common pathogens are same as thosethat cause brain abscess.Clinical features include fever, headache,and sometimes alteration in consciousness.CT or MRI is usually diagnostic. Subdural Empyema
Usuallyoccurs from spread of infection from meninges, middle ear, or sinuses. Pathogenscausing this unusual infection are same as those causing brain abscess.Fever, headache, vomiting, neck stiffness,papilledema, seizures, and alteration in consciousness are commonfindings.CT or MRI can be diagnostic. Surgicaldrainage confirms diagnosis and is therapeutic. Seizures
Status Epilepticus
Generalizedconvulsive status epilepticus is defined as single generalized seizurelasting >30 mins or recurrent seizures with failure toregain consciousness between them.Predisposing factors include febrileillness, bacterial meningitis, viral encephalitis, head trauma,underlying brain disorders, and noncompliance with anticonvulsanttherapy.Nonconvulsive generalized status epilepticusincludes absence status and almost always occurs in children withknown epilepsy.Frequently recurring complex partialseizures with failure of recovery between seizures constitute partialnonconvulsive status.Children with absence status or complexpartial status may be ambulatory but unable to follow complex commandsor converse appropriately. Postictal State
After generalized or complex partial seizure,child may be confused and difficult to arouse. Normal consciousnessis usually regained in a few hours.
Brain Tumor
Alterationof consciousness may occur with brain tumors because of seizures,increased intracranial pressure, tumor invasion of reticular activatingsystem, or hemorrhage.Location of tumor determines otherfindings.Tumors above tentorium can cause seizures,hemiparesis, speech problems, and intellectual difficulties, whereastumors below tentorium usually cause vomiting and ataxia.CT or MRI locates and defines extentof tumor.Histologic diagnosis is definitive.See Chap.25, Headache. Cerebrovascular Disorders
Cerebral thrombosis, embolism, or hemorrhagemay interrupt cerebral blood flow to produce stroke and alterationof consciousness.
Cerebral Thrombosis
Cerebralinfarction from occlusion of major cerebral artery usually producesfocal neurologic deficit without loss of consciousness, unless cerebraledema or hemorrhage produces significant increase in intracranialpressure.Common causes of stroke in pediatricpopulation are sickle cell disease, vasculitis, vascular dysplasia,and coagulopathy.Clinical features depend on cerebralartery involved. Usual finding is acute hemiparesis, which may beaccompanied by seizures, aphasia, hemianopia, and sensory changes.Evolution of thrombotic stroke usually occurs over minutes to hours.Thrombolytic therapy is only recommendedwithin 3 hrs of thrombotic or embolic stroke.Exclusion of intracranial hemorrhageby CT is important consideration if thrombolytic therapy is beingconsidered. Diffusion-weighted imaging on MRI may show signal changewithin few hours, indicative of infarction, whereas T2-weightedMRI takes 12–24 hrs to show signal change from infarction. CTmay not show low-density changes from infarction for 24–72hrs. Once it has been determined that infarction has occurred, specificcause must be investigated.Venous thrombosis (usually venous sinusthrombosis) leads to ischemia and sometimes infarction, usuallyhemorrhagic. Predisposing factors include infection (meningitis,sinusitis, mastoiditis, brain abscess), head trauma, dehydration,sickle cell disease, and drugs (L-asparaginase).Clinical presentation depends on underlyingdisease process and its extent. Clinical features include vomiting,headache, seizures, hemiparesis, and alteration in consciousness.CT or MRI can locate area of ischemiaor hemorrhage, but magnetic resonance venography is method of choiceto demonstrate venous thrombosis. Cerebral Embolism
Emboli fromorganized thrombus, fat, air, bacteria, or tumor can occlude cerebralartery.Causes include thrombosis (congenitalheart disease with right-to-left shunt lesions, atrial myxoma, cardiomyopathy,endocarditis, atrial fibrillation, arterial dissection), fat emboli(complications of fractures), air emboli (complications of cardiacor thoracic surgery), septic emboli (pneumonia or lung abscess),and tumor emboli that involve blood vessels.Embolic strokes usually evolve overminutes. Seizures and transient loss of consciousness may occurinitially, and headache, vomiting, and lassitude can follow. Focalneurologic findings include hemiparesis, aphasia, hemianopia, andsensory changes, depending on which cerebral artery is involved. Mostfrequent vessel involved is middle cerebral artery.CT or MRI can locate area of ischemiaor hemorrhage (see CerebralThrombosis). Specific cause must be investigated. Cerebral Hemorrhage
Most commoncause of cerebral hemorrhage is head trauma. However, spontaneous hemorrhagecan occur from rupture of a cerebral aneurysm or arteriovenous malformation.See Chap.25, Headache. Hydrocephalus
Acute hydrocephaluswith increased intracranial pressure may occur as consequence ofobstruction of ventricular pathways (e.g., enlarging brain tumorin posterior fossa).Headache, vomiting, lassitude, andalteration in consciousness are common findings. Increased intracranialpressure also may occur from malfunction of ventricular shunt.CT is diagnostic. With increased intracranialpressure, shunt radiographic series and CT should be performed immediatelyand neurosurgical consultation requested. Blood Pressure Disorders
Hypotension
May be dueto hypovolemia (diarrhea; vomiting; blood loss; plasma loss fromburns, hypoalbuminemia, or peritonitis; osmotic diuresis from diabetesmellitus), vasodilatation and pooling of blood in peripheral vasculature(septicemia, anaphylaxis, CNS or spinal injuries, drug ingestions),and depression of myocardial function (congenital heart disease,viral myocarditis, cardiomyopathy, arrhythmia, drug ingestion, complicationsof cardiac surgery).Early signs include tachycardia, mildtachypnea, decreased capillary refill (>2–3 secs)and orthostatic changes in BP. Skin becomes cool and pale, and decreasedperfusion of brain results in confusion, agitation, and finallycoma. Hypertensive Encephalopathy
Althoughthere is no absolute level of BP where hypertensive encephalopathyoccurs, rate of increase and level of BP are important determinants.After lowering BP, specific cause needs to be investigated.Clinical findings include headache,vomiting, visual disturbance, seizures, and alteration in consciousnessthat may proceed to coma.See Chap.32, Hypertension). Metabolic Disorders
Hypoxic-Ischemic Encephalopathy
Producesloss of consciousness within seconds. If adequate ventilation andcardiac action are restored within 3–5 mins, recovery isusually complete. If hypoxia persists >5 mins, permanent neurologicdeficit usually occurs, unless subnormal body temperatures havediminished rate of cerebral metabolism and prolonged tolerated periodof hypoxia.Most common cause in neonates is perinatalasphyxia. In infants and children, common causes include respiratoryarrest, near-drowning, strangulation, carbon monoxide poisoning,upper airway obstruction, aspiration of vomitus, and shock.Diagnosis depends on history of hypoxicepisode and evidence of reduced oxygenation of arterial blood. Ingeneral a partial pressure of arterial O2 of <50mm Hg causes confusion, and <20 mm Hg causes loss of consciousness.Most severely affected patients requiremechanical ventilation and usually have flaccid limbs and recurrentseizures. They may die within 1–2 days or survive in irreversiblecoma for variable periods of time. Acute Bilirubin Encephalopathy (Kernicterus)
Has becomemuch less common since anti-Rh immunoglobulin has been used to preventmaternal sensitization, but it still occurs.Most cases in past decade have occurredin infants with G6PD deficiency, in ill newborns with low bilirubinlevels, and in apparently normal term and near-term newborns withbilirubin levels much >30 mg/dL. In latter group,infants were breast-fed but had weight loss secondary to decreasedcaloric intake or dehydration, and just about all of them were ≤40wks' gestation.Initial manifestations include poorsucking, diminished movement, decreased muscle tone, and increasedsleepiness. Progression of illness causes irritability, minimalfeeding, high-pitched cry, and increased muscle tone, which mayinclude arching of neck (retrocollis) and back (opisthotonus). Severely illinfants have shrill cry, increased muscle tone, seizures, and coma. Diabetic Ketoacidosis
Complicationof diabetes mellitus.Possible causes in individuals withknown diabetes mellitus include inadequate insulin dosage, failureto take proper dose of insulin, and intercurrent infection.Vomiting, abdominal pain, and hyperpneaare frequent findings. Alteration in consciousness occurs in severecases.Presence of hyperglycemia, glycosuria,ketonuria, and metabolic acidosis (arterial pH <7.25 andserum bicarbonate <15 mEq/L) confirm diagnosis. Hypoglycemia
Blood glucoseconcentration <30 mg/dL may produce confusionand seizures. If blood glucose falls to <10 mg/dL,loss of consciousness may occur.Clinical presentation of hypoglycemiausually unfolds over 30–60 mins. If blood glucose is low,venous blood should be drawn for further studies and glucose shouldbe given immediately.See Chap.59, Seizures. Hypothermia
Definedas core temperature <35DEGC (95DEGF).Common causes include exposure to lowenvironmental temperature, cold water immersion, septicemia, andanorexia nervosa.Mental status may be normal with mildhypothermia but deteriorates until coma occurs at about 27DEGC. Heat-Related Illness
Includesheat cramps, heat exhaustion, and heat stroke.Heat cramps are muscle cramps occurringduring severe work.Individuals with heat exhaustion experienceheadache, vomiting, and severe thirst from working in hot environmentwithout adequate replacement of water and salt. Body temperatureis usually <39DEGC.With heat stroke, body temperatureis >41DEGC and CNS dysfunction (confusion, agitation, seizures,coma) and circulatory collapse may occur. Hepatic Coma
May occurwith any form of severe acute or chronic liver disease. Intercurrentinfection, GI bleeding, and electrolyte imbalance with hypokalemiamay precipitate hepatic coma in those with severe liver disease.Clinical findings include progressivejaundice, alteration in consciousness, and preceding asterixis.Usual lab findings include elevationof serum aminotransferases and ammonia along with primarily conjugatedbilirubin. Prothrombin time is prolonged and serum albumin is decreased.Blood ammonia is usually >200 μmol/L,and severity of neurologic disturbance parallels ammonia levels. Reye Syndrome
Due to diminisheduse of aspirin in recent years, incidence has decreased markedly.Onset of persistent vomiting is usuallyfirst sign and occurs during week after viral illness or varicella.Confusion and listlessness may progress to disorientation and combativeness.Seizures may occur, but fever is unusual. Hypoglycemia is frequentfinding, especially in infants <1 yr. Decorticate or decerebrateposturing and loss of brainstem function due to cerebral edema mayoccur with disease progression.Viral prodrome, behavior changes, unexplainedvomiting, and characteristic chemical profile (increase in serumaminotransferases, ammonia, and prothrombin time with minimal changein bilirubin) suggest diagnosis. Liver biopsy is usually diagnosticbut may not be necessary in mild cases. Certain metabolic disorders,such as defects in fatty acid oxidation, may mimic the condition. Uremia
Alteration in consciousness may occur, butprecise mechanism is unknown.
Inborn Errors of Metabolism
Besides alteration of consciousness, clinicalfeatures include poor feeding, vomiting, seizures, and delayed neurologicdevelopment. Hyperammonemia occurs in many of these disorders.
Maple Syrup Urine Disease
Recognizedas autosomal-recessive disorder caused by deficiency in activityof branched-chain alpha-ketoacid dehydrogenase complex.Onset of classic form is usually infirst or second week of life, with poor feeding, seizures, and alterationin consciousness.Urine has characteristic odor of maplesugar and is positive for ketones.Subsequent episodes of metabolic acidosisand disturbed consciousness may occur during catabolic period orwith excess protein intake.Affected children usually have psychomotorretardation.Analysis of plasma amino acids revealsincreased concentrations of isoleucine, leucine, and valine.Enzyme assay of cultured fibroblastsor leukocytes is definitive. Nonketotic Hyperglycinemia
Mutationsin several genes in glycine cleavage enzyme system can cause thisautosomal-recessive disorder.Onset is typically in first few daysof life, with hypotonia, myoclonic jerks, alteration in consciousness,and often hiccups. Clinical course is characterized by intractableseizures and severe developmental delay.Lack of hypoglycemia, metabolic acidosis,ketosis, hyperammonemia, hepatocellular dysfunction, and cardiac,renal, or hematologic abnormalities suggests diagnosis.Though serum and urinary glycine concentrationsare usually increased, elevation of CSF glycine is considered diagnostic. Hyperammonemic Disorders
Urea Cycle Defects
Urea cycleis major pathway for conversion of ammonia to urea. Enzyme deficiencies inthis pathway lead to production of excessive amounts of ammonia.All are autosomal-recessive disordersexcept for ornithine transcarbamylase deficiency, which is X-linkeddisorder.These defects commonly present duringfirst week of life, with poor feeding, vomiting, tachypnea, seizures,and alteration in consciousness, except for arginase deficiency,which usually appears in later infancy. Infants who survive neonatalperiod usually have developmental delay and psychomotor retardation. Carbamyl Phosphate Synthetase Deficiency
Gene locushas been mapped to chromosome 2q35.Serum levels of citrulline and arginineand urinary level of orotic acid are low.Liver biopsy with enzyme assay is definitive. Ornithine Transcarbamylase Deficiency
Althoughaffected boys become symptomatic in neonatal period, girls who arecarriers usually become symptomatic in childhood.Clinical features include feeding difficulty,failure to thrive, intermittent ataxia, and alteration in consciousness.Plasma citrulline concentration is low, whereas urinary orotic acidconcentration is high.Liver biopsy with enzyme assay is definitive. Argininosuccinic Acid Synthetase Deficiency (Citrullinemia)
Gene locushas been mapped to chromosome 9q34.3 clinical phenotypes have been described.In neonates presentation is acute andsimilar to that of ornithine transcarbamylase deficiency.In infants onset is gradual with poorfeeding, vomiting, hepatomegaly, and psychomotor retardation.In children episodic hyperammonemiamay cause vomiting and seizures.Marked increase in serum citrullineconcentration (>1,000 μM) is diagnostic. Enzymeassay of liver tissue or cultured fibroblasts is definitive. Argininosuccinase Deficiency (Argininosuccinic Aciduria)
Gene locushas been mapped to chromosome 7.Can present in neonatal period withacute encephalopathy or in infancy with hepatomegaly, seizures,ataxia, and developmental delay.Some children have short brittle hair(trichorrhexis nodosa).Plasma citrulline concentration ismoderately increased (100–300 μM).Presence of high serum and urine concentrationsof argininosuccinic acid is diagnostic. Enzyme can be assayed inliver or skin fibroblasts. N-Acetylglutamate Synthetase Deficiency
Catalyzesformation of N-acetylglutamate from glutamate and acetyl-CoA andis required activator of carbamyl phosphate synthetase. Only a fewcases have been reported.Usual lab findings are absent or traceserum citrulline, low serum arginine and ornithine, increased serumalanine and glutamine, and decreased urinary orotic acid. Liverbiopsy that shows decreased enzyme activity confirms diagnosis. Arginase Deficiency (Argininemia)
Gene locushas been mapped to chromosome 6q23.Usually presents in infancy.Characteristic features include recurrentvomiting, spastic diplegia, seizures, and developmental delay. Symptomatichyperammonemia may progress to encephalopathy.Serum citrulline concentration is normalor mildly increased. High serum arginine concentration is diagnostic.Enzyme assay of erythrocytes or liver tissue is confirmatory. Organic Acid Disorders
Propionic, Isovaleric, and Methylmalonic Acidemias
Autosomal-recessiveand clinically indistinguishable.Hyperammonemia, metabolic acidosiswith anion gap, hypoglycemia, and urinary ketones usually occur.Psychomotor retardation occurs in most affected individuals.Urinary organic acid analysis showstypical organic acid profile of specific disorder. Definitive diagnosisis made by analysis of specific enzyme activity in cultured skinfibroblasts or sometimes by specific mutation analysis.Propionic acidemia is due to deficiencyin activity of propionyl-CoA carboxylase, which catalyzes conversionof propionyl CoA to methylmalonyl CoA.Gene locus of type I has been mapped to chromosome13q32; gene locus of type II has been mapped to chromosome 3q21-22.Excessive amounts of propionic acidand glycine in blood and urine suggest diagnosis. Presence of excessiveamount of methylcitrate in urine is diagnostic. Deficiency in activity of isovalerylCoA dehydrogenase, which catalyzes conversion of isovaleryl CoAto 3-methylcrotonyl CoA, causes isovaleric acidemia.Gene locushas been mapped to chromosome 15q14-q15.Odor of sweaty feet produced by isovalericacid has been described.Detection of excessive amounts of isovalerylglycineand 3-hydroxyisovaleric acid in urine is diagnostic. Methylmalonic acidemias are group ofdisorders in which methylmalonic acid accumulates in body fluidsbecause of deficiency in activity of methylmalonyl-CoA mutase. Thisenzyme requires cobalamin (vitamin B12) ascofactor for activity.Classic form of methylmalonic academia, whosegene locus has been mapped to chromosome 6p21, is not responsiveto pharmacologic doses of vitamin B12.In another milder form of disorderthat presents later in infancy with vomiting and delayed growthand development, pharmacologic doses of vitamin B12 contributeto dramatic improvement.In either form, excessive amount ofmethylmalonic acid is found in urine, which is diagnostic. Glutaric Aciduria, Type II (Multiple Acyl-CoA DehydrogenaseDeficiency)
Can occurfrom deficiency in alpha or beta subunits of electron transfer flavoprotein ordeficiency of electron flavoprotein dehydrogenase.Genetic transmission is autosomal-recessive,and gene locus for each defect has been mapped to different chromosomes.Typical clinical features in neonatesare vomiting, tachypnea, hepatomegaly, sweaty feet odor, and alterationof consciousness.Biochemical abnormalities include hyperammonemia,hypoglycemia, metabolic acidosis without ketosis, and large urinaryexcretion of glutaric, lactic, ethymalonic, butyric, isobutyric,2-methyl-butyric, and isovaleric acids.Specific defects may be demonstratedin cultured fibroblasts. Multiple Carboxylase Deficiency
2 basictypes of multiple carboxylase deficiency are holocarboxylase synthetasedeficiency and biotinidase deficiency.Gene locus of former is chromosome21q22.1, whereas that of latter is chromosome 3p25.Basic defect involves metabolism ofbiotin, vitamin necessary for action of carboxylases.Onset of holocarboxylase synthetasedeficiency is in first week of life with tachypnea, vomiting, hypotonia,seizures, and alteration of consciousness.Metabolic features include hyperammonemia,metabolic acidosis, ketosis, hypoglycemia, and organic acidemiawith increased serum concentrations of lactate, propionate, andbeta-methylcrotonate.Enzyme defect can be demonstrated incultured fibroblasts and leukocytes. Biotinidase deficiency typically presentsduring first 3 mos of life.Clinical features are similar to those of holocarboxylasesynthetase deficiency. In addition, dry skin rash, alopecia, hearingloss, optic atrophy, developmental delay, and ataxia may occur.Diagnosis is confirmed by low serum biotinidase level. Pyruvate Dehydrogenase Complex Deficiency
Deficiencyof any of enzymes involved in pyruvate dehydrogenase complex results inlactic acidosis and CNS dysfunction, including alteration in consciousness.See Chap.4, Ataxia. Pyruvate Carboxylase Deficiency
Pyruvatecarboxylase catalyzes conversion of pyruvate to oxaloacetate.Clinical features in newborn includetachypnea, hypotonia, seizures, and alteration of consciousness.Survivors usually have episodic ataxia, seizures, and psychomotordelay.Less severe form may occur in infancywith milder lactic acidosis and developmental delay.Usual lab findings are increase inserum concentration of ammonia, lactate, pyruvate, alanine, citrulline,and lysine. Measurement of enzyme activity in skin fibroblasts orliver is diagnostic. Fatty Acid Oxidation Defects
Most commonis medium-chain acyl-CoA dehydrogenase deficiency, but others includeshort-chain, long-chain, and very-long-chain acyl-CoA dehydrogenasedeficiencies.May present with vomiting, hypotonia,seizures, cardiac dysfunction, and alteration of consciousness.Usual metabolic findings include hyperammonemia,hypoglycemia without ketones, metabolic acidosis, and dicarboxylicaciduria (fatty acid intermediates).Analysis of plasma acylcarnitine profilesin these disorders establishes diagnosis. Demonstration of enzymedefect in leukocytes or fibroblasts is definitive. Respiratory Chain Disorders
Defectsin respiratory chain involving complexes I, III, and IV can causeseizures, weakness, hypotonia, developmental delay, and alterationin consciousness.Hyperammonemia often occurs, and lactate/pyruvateratio is usually abnormally increased (>20).Other mitochondrial disorders [e.g.,MELAS (mitochondrial myopathy, encephalopathy, lactic acidosis,strokelike episodes)] may cause alteration of consciousnesswithout associated hyperammonemia. Other common presenting symptomsand signs of these disorders include developmental delay or regression,seizures, and hypotonia.Muscle biopsy including electron microscopyand respiratory chain enzyme analysis is diagnostic. Lysinuric Protein Intolerance
Definedas autosomal-recessive disorder caused by mutations in amino acidtransporter gene SLC7A7, whose locus has been mapped to chromosome14q11.2. As a result, intestinal membrane transport of lysine, arginine,and ornithine is defective.Onset is usually in infancy or childhood,with poor feeding, vomiting, hypotonia, and alteration of consciousness.Hyperammonemia is prominent finding.Serum concentrations of the above aminoacids are low, while their urinary excretion is high. Hyperornithinemia-Hyperammonemia-Homocitrullinuria Syndrome
Definedas autosomal-recessive disorder with impaired transport of aminoacid ornithine into mitochondria via ornithine transporter protein.Gene locus has been mapped to chromosome13q14.May present in neonatal period or inchildhood with vomiting, seizures, and alteration in consciousnessrelated to hyperammonemia.Diagnosis is confirmed by finding increasedserum concentration of ornithine and increased urinary concentrationof homocitrulline. Transient Hyperammonemia of Prematurity
Usuallypresents on first or second day of life, often before any protein-containing feedingor IV solution has been given.Usual findings include impaired eyemovements, fixed dilated pupils, seizures, alteration of consciousness,and marked hyperammonemia.Spontaneous resolution usually occursover 1–2 wks.Pathogenesis unknown. Other Metabolic Disturbances
Hyponatremia,hypernatremia, hypocalcemia, hypercalcemia, hypomagnesemia, and hypermagnesemiamay cause alteration in consciousness.Serum sodium, calcium, and magnesiumconcentrations should be measured.See Chap.59, Seizures. Poisoning, Drug Overdose, and Intoxication
Many substances in high enough doses cancause toxic reactions, including alteration in consciousness.
Carbon Monoxide
Should besuspected when individual has inhaled smoke from fire, automobileexhaust fumes in closed space, or fumes from faulty home heater.Carbon monoxide binds much more tightlyto Hgb than does O2 and thus decreases O2-carryingcapacity of blood. Concentration of carboxyhemoglobin in blood ofnormal individuals is <1%. Levels of 20–40% produceconfusion, nausea, and vomiting. Incoordination, weakness, and lossof recent memory occur with levels of 40–60%,whereas seizures and coma are almost certain with levels >60%.Simultaneous onset of similar symptomsin other individuals with same exposure is clue to this diagnosis. Sedative-Hypnotic Drugs
Includebarbiturates and benzodiazepines, which depress CNS by depressingreticular activating system.Overdose of up to 5 times hypnoticdose of barbiturate may produce headache, drowsiness, slurred speech,confusion, and ataxia. Ingestion of 10 times hypnotic close mayproduce decreased consciousness and respiratory depression.Pupillary constriction is usual, butdilation sometimes occurs. Overdose of benzodiazepine (diazepam,chlordiazepoxide, flurazepam, lorazepam, triazolam) may producefindings similar to ethanol ingestion: euphoria, disinhibition,and ataxia. Severe overdose may cause bradycardia, hypothermia,miosis, hypotension, and coma.History of ingestion or toxicologyurine screen confirms diagnosis.Flumazenil, a benzodiazepine receptorantagonist, may be used to reverse benzodiazepine-induced coma andis important diagnostic and therapeutic agent in comatose childrenwith possible overdose. Opiates
Definedas substances derived from the opium poppy. Codeine and morphineare natural derivatives. Heroin, oxycodone, hydromorphone, and oxymorphoneare semi-synthetic derivatives, whereas meperidine, methadone, propoxyphene,pentazocine, and fentanyl are completely synthetic derivatives.Effects of opiates include analgesia,drowsiness, nausea and vomiting, constipation, and mood changes.Overdose may cause respiratory depression and alteration of consciousness.In the absence of history of ingestion, the combination of miosis,respiratory depression, and coma should suggest the diagnosis. Otherfindings may include bradycardia, hypothermia, hypotension, seizures,and pulmonary edema.History, naloxone reversal of clinicalsigns, or toxicology screening of urine is diagnostic. Alcohols
Intoxicationmay produce excitement, exhilaration, loquacity, slurred speech,loss of restraint, drowsiness, incoordination of movement and gait,and decreased consciousness.Prototype alcohol ingestion is withethyl alcohol. Other alcohols that also may produce alteration ofconsciousness are ethylene glycol, isopropyl alcohol, and methylalcohol (methanol). Ethyl Alcohol (Ethanol)
Distilledspirits contain 40–50% ethanol; wine, 10–20%;and beers, 2–6%. Many household products (e.g.,mouthwashes, colognes, after-shave lotions, and some liquid medications)also contain ethanol.After significant ingestion, nauseaand vomiting occur. Ethanol concentrations in the blood of 100–150mg/dL produce slurred speech, incoherence, incoordination,ataxia, and impaired vision. Levels >300 mg/dLmay produce coma.Infants and toddlers have a differentclinical course than older children and adolescents. Once ethanollevels are >50–100 mg/dL, hypoglycemia,hypothermia, and coma can develop.History, smell of the breath, or quantitativeserum level is diagnostic. Ethylene Glycol
Componentof windshield de-icer and automobile antifreeze solutions.Ingestion produces ethanol-like intoxication,with nausea and vomiting, drowsiness, confusion, slurred speech,ataxia, and metabolic acidosis.Production of oxalic acid from ethyleneglycol results in calcium oxalate crystal deposition throughoutthe body, including brain, heart, and kidney tubules.Hypocalcemia may be significant enoughto produce tetany and disturbances of cardiac conduction.History or quantitative serum levelis diagnostic. Isopropyl Alcohol (Rubbing Alcohol)
Overdoseproduces ethanol-like intoxication, with nausea and vomiting, confusion, andataxia. Severe overdose may produce myocardial depression, hypotension,and shock.Hypoglycemia may occur in young children.Because the metabolite of isopropylalcohol is acetone and not an acid, acetonuria and absence of metabolicacidosis characterize this type of intoxication.History or quantitative serum levelis diagnostic. Methyl Alcohol (Methanol)
Used asantifreeze (windshield washer fluid and gasoline) and as solventin many industrial and home products (varnishes and paint thinners).Its metabolites, formaldehyde and formicacid, are highly toxic.Clinical effects usually occur within8–24 hrs of ingestion. Manifestations of severe overdoseinclude vomiting, abdominal pain, hyperpnea, impaired vision, seizures,coma, and metabolic acidosis with increased anion gap.History or quantitative serum levelis diagnostic. Anticonvulsants
Phenytoin
Drowsiness,slurred speech, nystagmus, and ataxia occur with mild ingestion.With more severe ingestion, tremor, choreoathetosis, and confusioncan occur, but coma is unusual.History or quantitative serum levelis diagnostic. Carbamazepine
Effectsof toxic ingestion include nystagmus, ataxia, and anticholinergicmanifestations, which may be followed by seizures and coma.History or quantitative serum levelis diagnostic. Valproic Acid
Toxic ingestionmay produce pinpoint pupils and drowsiness, which may progress to coma.History or quantitative serum levelis diagnostic. Phenothiazines
Commonlyprescribed major tranquilizers that are also used to treat nauseaand vomiting. Prototype is chlorpromazine.In mild intoxication, slurred speech,sedation, and ataxia occur. Anticholinergic findings include constipation,blurred vision, and urinary retention. With more serious intoxication,muscle stiffness, dystonic reactions, arrhythmias, hypotension,and alteration of consciousness may occur.Qualitative UA confirms diagnosis. Tricyclic Antidepressants
Ingestionof 10–20 mg/kg of most tricyclic antidepressantsis moderate to severe exposure. Ingestion of 35–50 mg/kgmay result in death.Prototype is amitriptyline hydrochloride.Toxic effects produce drowsiness, slurredspeech, and ataxia. Anticholinergic signs (e.g., flushed skin, tachycardia,and dilated pupils) also may occur. Hallucinations, seizures, coma,and respiratory arrest can follow.QRS duration of >100 msecsin the limb leads is indication of serious overdose; complete heartblock and ventricular tachycardia may occur.History, quantitative serum level,or qualitative UA confirms diagnosis. Anticholinergic Drugs
Block theaction of acetylcholine at CNS cholinergic receptors and at muscarinicreceptors (parasympathetic nerve endings and sympathetic nerve endingsto sweat glands). Some drugs (atropine, scopolamine, tricyclic antidepressants,phenothiazines, antihistamines) as well as certain plants and mushroomshave anticholinergic properties.Clinical manifestations of mild overdoseinclude hyperpyrexia, tachycardia, mydriasis, flushing, dry mucousmembranes, hot dry skin, urinary retention, decreased sweating,drowsiness, excitement, confusion, disorientation, visual hallucinations,and anxiety. Large overdose may cause seizures, arrhythmias, coma,and shock.History or qualitative UA confirmsdiagnosis.Physostigmine can reverse mental statuschanges caused by anticholinergic drugs but should be used withcaution because it can produce bronchospasm, bradycardia, hypotension,and seizures. Salicylates
Prototypeis acetylsalicylic acid (aspirin), although other chemical formsof salicylates exist in many different products.Methyl salicylate (oil of wintergreen)is especially dangerous because of its high concentration of salicylate(1 mL contains 1.4 g of aspirin).All forms of salicylates produce similarclinical picture. With mild poisoning, nausea and vomiting, fever,hyperpnea, and confusion occur. Severe poisoning produces seizures,coma, and respiratory or cardiovascular collapse.Metabolic acidosis with increased aniongap and a respiratory alkalosis are characteristic of salicylateintoxication.If <150 mg/kg ofsalicylate is acutely ingested, determination of serum level isunnecessary. History of single ingestion of 150–300 mg/kgsalicylate signifies mild intoxication, whereas ingestion of >300mg/kg signifies serious intoxication. With acute overdose,a nomogram may be used to estimate severity of poisoning. Bloodlevel >100 mg/dL is indicative of serious intoxication.In chronic intoxication, impossibleto establish correlation between serum concentration and severityof illness. Lead
Acute severepoisoning may cause encephalopathy but is rare now because of routine leadscreening.Risk of acute encephalopathy increaseswith blood lead level >80 μg/dL.Manifestations of encephalopathy includevomiting, ataxia, seizures, and impaired consciousness, which mayprogress to coma with increased intracranial pressure. Organophosphates
Ingestion,inhalation, or skin exposure produce various toxic effects.Organophosphates irreversibly phosphorylatethe enzyme acetylcholinesterase, which results in excessive accumulationof acetylcholine in CNS, at cholinergic junctions in autonomic nervous system(causing muscarinic effects), and in skeletal muscle or autonomicganglia (causing nicotinic effects).Manifestations are CNS (headache, confusion,emotional lability, ataxia, seizures, coma), muscarinic (salivation,lacrimation, urinary incontinence, vomiting, diarrhea, abdominalcramping), and nicotinic (sweating, tremors, weakness, muscle twitching).Miosis, bradycardia, hypotension, rhinorrhea, and wheezing alsomay occur.History of exposure and characteristicfindings are diagnostic. Decreased RBC cholinesterase level confirmsdiagnosis. Amphetamines
Stimulaterelease of biogenic amines from presynaptic neurons and have agonistaction on postsynaptic catecholamine receptors.Can cause nausea and vomiting, abdominalcramps, dry mouth, sweating, tremors, tachycardia, hyperpyrexia,hypertension or hypotension, dilated pupils, cardiac arrhythmias,excitation, confusion, hallucinations, paranoid delusions, seizures,and coma.Peak serum level is 1–2 hrsafter acute ingestion.History or toxicologic UA is diagnostic. Cocaine
Importanteffects are interference with catecholamine, dopamine, and serotonintransmission in CNS and blocking of catecholamine reuptake at adrenergicnerve endings.Clinical effects appear within minutesif injected or smoked and within 1 hr if ingested.Effects on CNS include agitation, euphoria,tremor, twitching, and mydriasis. Severe overdose may produce respiratorydistress, hyperpyrexia, hypertension, stroke, myocardial infarction,seizures, and coma.History or qualitative UA is diagnostic. Hallucinogens (Psychedelics)
Commonlyused hallucinogens include phencyclidine (angel dust), lysergicacid diethylamide (LSD), and marijuana. Can produce illusions, hallucinations,delusions, and paranoid ideation as well as vivid and unusual visualexperiences with diminished control over what is experienced.Phencyclidine can produce slurred speech,nystagmus, and staggering gait in small doses. Fever, hypersalivation,repetitive movements, and muscular rigidity can occur with moderatedoses. Severe intoxication can produce seizures, coma, and respiratoryarrest. History or qualitative UA is diagnostic.Somatic effects of LSD are sympathomimeticand include pupillary dilatation, hypertension, tachycardia, hyperpyrexia,tachycardia, and hyperreflexia. CNS effects include euphoria, emotional lability,perceptual changes in vision and hearing, delusional ideation, andbody distortion. LSD is found in such low concentrations that identificationis difficult.Most prominent symptoms of marijuanause involve CNS and cardiovascular system. Marijuana may produceconfused and disorganized thinking, impaired short-term memory,and euphoria followed by anxiety and panic. Larger doses may causehallucinations, delirium, and paranoid feelings. Tachycardia andhypertension also may occur. History or qualitative UA is diagnostic. Iron
Ingestionof >20 mg/kg may produce symptoms, whereas >50mg/kg often produces toxic effects. Serum iron levels of >300 μg/dLare toxic; those >500 μg/dL are usuallyassociated with severe poisoning.Overdose has GI, cardiovascular, andneurologic effects. Vomiting and diarrhea may be followed by GIbleeding, hypotension, pulmonary edema, renal tubular necrosis,liver dysfunction, coagulopathy, seizures, and coma.History and serum iron level are diagnostic. Hydrocarbons
Can be dividedinto 2 groups: aliphatic (petroleum distillates) and aromatic (benzene, xylene,toluene, turpentine, halogenated forms). Aliphatic hydrocarbonsare rapidly absorbed from respiratory tract but poorly absorbedfrom GI tract, whereas aromatic hydrocarbons are rapidly absorbedfrom either route.Severe ingestion of aliphatic or aromatichydrocarbon may cause nausea and vomiting, cough, dyspnea, aspirationpneumonia, and fever. May produce alteration in consciousness rangingfrom confusion to coma.History confirms diagnosis. Clonidine
Acts centrallyas alpha2 receptor agonist to reduce sympathetic outflow,which produces mild sedation and decrease in BP and heart rate.Initial manifestations include changesin mental status that may range from lethargy to coma. Hypothermia,miosis, and respiratory depression also may occur. Clonidine-inducedhypertension is uncommon, and central effect may be overridden byalpha-adrenergic effects at peripheral vascular receptors.No available blood tests.Intoxication resembles opiate overdose,and lack of response to naloxone helps distinguish clonidine overdosefrom opiate overdose. Diagnostic Approach
When individualpresents with alteration of consciousness, diagnosis and treatment mustproceed concurrently, not serially.ABCs of resuscitation (airway, breathing,circulation) take precedence over other diagnostic and therapeuticmeasures. Airway must be cleared, and oxygen should be given bymask and bag ventilation.Failure of adequate ventilation requiresintubation.Hypotension or shock should be treatedwith volume expansion.With suspected or known head or necktrauma, head should be stabilized until lateral cervical spine radiographcan be performed to determine whether cervical spine injury hasoccurred.Level of consciousness and responsiveness,motor function, pupil size and responses, and extraocular movementsshould be evaluated. Presence or absence of meningeal signs as wellas focal hemispheric or brainstem findings also should be noted.Unless diagnosis has been establishedby history and physical exam, a number of tests need to be performed.Measurementof blood glucose should be done immediately at bedside.Blood should be sent for CBC with differential;serum electrolytes, glucose, creatinine, calcium, magnesium, ammonia;blood urea nitrogen; liver function tests; blood culture; and toxicology screen.Urine should be obtained for UA, urineculture, and toxicology screen. Vital Signs
Respiratory Rate and Pattern
Dyspneaand/or tachypnea may occur with pneumonia, any cause ofmetabolic acidosis, and lesions of lower midbrain–upperpontine tegmentum.Slow, irregular respirations may beassociated with drug intoxication, septicemia, and intracranialmass lesion. With acute head injury or diffuse brain damage of anycause, abnormal breathing patterns often overlap, making it difficultto relate specific pattern with discrete location of brain damage. Heart Rate
Bradycardia,if associated with hypertension and periodic breathing, suggestsincreased intracranial pressure.Tachycardia may occur with hypovolemicshock (dehydration, blood loss, diabetic ketoacidosis) and anticholinergicpoisoning. Blood Pressure
Hypertensionmay occur with increased intracranial pressure and with drug overdoses (amphetamines,cocaine, phencyclidine).Hypotension may occur with hypovolemia(fluid losses from gastroenteritis, acute blood loss, diabetic ketoacidosis),septicemia, adrenal insufficiency, and ingestion of alcohol or barbiturates. Temperature
Hyperpyrexiamay indicate presence of infection (bacterial meningitis, septicemia, pneumonia),heat stroke, or cocaine overdose. Although uncommon, brain lesionthat has disturbed temperature-regulating center also may producehyperpyrexia.Hypothermia may occur with severe hypovolemiaas well as with barbiturate or alcohol ingestion. Level of Consciousness and Responsiveness
Level ofconsciousness can be determined by noting degree of arousability.Response to name, simple commands,or painful stimuli (sternal pressure or pinching side of neck, innerarm, or thigh) can be used to evaluate degree of unresponsiveness.Eye opening or any form of speakingincluding grunting or groaning suggests some degree of functionof reticular activating system.Speech and purposeful withdrawal orlocalization of painful stimuli are signs of intact cortical function. Motor Function
Restlessmovements of arms and legs, variable resistance to passive movement,complex avoidance movements, and discrete protective movements generallyindicate intact corticospinal tracts, whereas asymmetry of functionmay indicate hemiparesis.Presence of posturing should be noted.Decorticate posturing consists of flexion of arms, wrists, and fingerswith adduction of upper extremities, and extension, internal rotation,and plantar flexion of lower extremities. Associated with diffusedamage to cerebral cortex and subcortical white matter or basalganglia. Decerebrate posturing, which consists of arm and hand extensionand back arching, is associated with extensive midbrain damage.Flaccid extremities and absence ofany motor response indicate further depression of brainstem function. Pupil Size and Responses
Exam ofpupils and their reactivity help determine level and location oflesions affecting reticular activating system in brainstem. Anyreactivity signifies intact parasympathetic and sympathetic pathwaysof oculomotor nerve. Bilateral lesions of midbrain that interruptthis pathway produce dilated unreactive pupils. Pontine lesionsproduce miotic pupils with only mild reaction to light. Unilateral pupillarydilatation suggests third nerve compression and impending uncalherniation.Generally, pupils remain reactive withmetabolic or toxic causes of coma. Exceptions include atropine orscopolamine poisoning, which causes dilated unreactive pupils; glutethimidepoisoning, which may cause medium to large unreactive pupils; opiatepoisoning (morphine, heroin), which causes pinpoint pupils withonly slight constriction to light; and severe anoxia with cardiacarrest, which produces fixed and dilated pupils. Miosis is usuallyseen with opiate, organophosphate, or clonidine overdosage, whereasmydriasis is usually seen with anticholinergic poisoning (tricyclicantidepressants) or with stimulant overdosage (amphetamines, cocaine). Extraocular Movements
Evaluationof eyes at rest, abnormal spontaneous eye movements, and ocularresponse to labyrinthine function provide important informationin assessment of alteration of consciousness.Cerebral lesions (usually frontal lobe)usually produce conjugate deviation of eyes to side of lesion andnormal labyrinthine responses, whereas unilateral pontine lesionsusually produce eye deviation away from side of lesion as well asabnormal labyrinthine responses. Midbrain lesions that involve oculomotornucleus or nerve or pontine lesions involving abducens nucleus ornerve may cause abduction of ipsilateral eye.Ocular response to vestibular stimulationalso helps evaluate integrity of brainstem function in childrenwith alteration of consciousness. Brainstem function is intact whenice water injection of 50 mL into external auditory canal with headflexed to 30 degrees produces conjugate horizontal eye deviationto side of injection and horizontal rapid nystagmus to oppositeside. Absence of such reflexes indicates severe brainstem dysfunction.Oculocephalic (doll's eye)reflex is also used to produce vestibular stimulation, but it iscontraindicated with suspected cervical spine injury. Head is rotatedfrom side to side and positive response indicating intact brainstemfunction is conjugate horizontal eye movement in opposite directionfrom head turn. Further Evaluation and Specific Diagnosis
Vital signsand assessments already described usually indicate whether any focal hemisphericor brainstem dysfunction exists. Final task is to make definitivediagnosis.Focal neurologic signs including asymmetricmovements and abnormal postures usually signify structural lesionin cerebral hemisphere, which also may affect brainstem function.Lesions above tentorium may cause alterationof consciousness by depression of large portions of both cerebralhemispheres, whereas lesions below tentorium (usually tumor or collectionof blood in posterior fossa) depress consciousness by compressionof brainstem structures.Presence of increased intracranialpressure may lead to central or uncal cerebral herniation. Centralherniation refers to rostrocaudal pattern of deterioration withloss of consciousness and irregular respirations followed by bilateraldilated unresponsive pupils and either decorticate or decerebrateposturing. Uncal herniation occurs more suddenly with loss of consciousnessand unilateral dilated pupil occurring almost simultaneously.Hemiparesis or hemiplegia may occurcontralateral to lesion.In cases of suspected structural lesion ± historyof head trauma, CT should be performed immediately. When herniationor impending herniation is suspected, patient should be intubated,hyperventilated, and given mannitol to acutely decrease increasedintracranial pressure prior to CT.Meningeal signs (stiff neck, Kernigor Brudzinski signs) commonly occur with bacterial meningitis andsubarachnoid hemorrhage. Lumbar puncture should be performed withsuspected bacterial meningitis or viral encephalitis. CT shouldbe performed first to rule out mass lesion in individuals with focalneurologic signs or symptoms of coma. If patient is unstable, appropriateantibiotic therapy should be given for suspected bacterial meningitisafter blood culture has been drawn, and lumbar puncture may be deferreduntil child is stable. In individuals with suspected subarachnoidhemorrhage and increased intracranial pressure, CT should be performedimmediately.Individuals without meningeal or focalneurologic signs may have head injury, drug intoxication, seizure,or metabolic disorder. Precise drug history is important but oftenis unavailable. 3 specific antidotes are available:Naloxone foropiate overdosePhysostigmine for anticholinergic poisoningFlumazenil for benzodiazepine overdose Metabolic causes of coma tend to producesymmetric hemispheric responses with normal brainstem function.With hyperammonemia in neonatal period,urea cycle defects and organic acid disorders should be suspected. Fig.3.1 (Adapted from Batshaw ML. Inborn errors of ureasynthesis. Ann Neurol 1994;35:137, with permission.) provides schemeto determine cause of hyperammonemia in neonates. Measurement ofserum ammonia, amino acids, lactate, and pyruvate, as well as urinaryorganic acids and orotic acid, will identify virtually all of geneticcauses of hyperammonia in this age group. Plasma acylcarnitine profilecan help diagnose various fatty acid oxidation defects. In a fewinstances (carbamyl phosphate synthetase and N-acetylglutamate synthetasedeficiencies), specific enzyme analysis must be performed to confirmdiagnosis. In infantsand children with hyperammonemia, scheme used for neonates can befollowed. However, if urinary organic acids are normal, prothrombintime and serum bilirubin should be measured. If these results areabnormal, liver disease, drugs, hepatotoxins, and Reye syndromeshould be considered. Also, if plasma citrulline is normal, plasmaarginine should be measured. Increase in plasma arginine signifiesarginase deficiency. Low or normal plasma arginine suggests 2 possibilities:lysine protein intolerance or hyperornithinemia-hyperammonemia-homocitrullinemiasyndrome. Increase in urinary lysine signifies lysine protein intolerance,whereas increase in plasma ornithine and urinary homocitrulline signifieshyperornithinemia-hyperammonemia-homocitrullinemia syndrome. Otherinvestigations depend on clinical findings and results of abovetests. >>>'>>>>>>>>>
» READ BOOK EXCERPT ONLINE »
Source: The Diagnostic Approach to Symptoms and Signs in Pediatrics, 2006
MUSCULAR ATROPHY:
Approach to the Diagnosis
(Differential Diagnosis in Primary Care)
Focal atrophy of a muscle often means a damaged peripheral nerve or
root. If there are visible fasciculations, a lesion of the spinal cord or
root is most likely. Electromyography will determine which portion of the
nerve is affected. It will also be helpful in diagnosing muscle disease.
Muscle biopsy is valuable in ruling out trichinosis, dermatomyositis,
or muscular dystrophy. If there are
fasciculations, a spine x-ray, spinal tap, and myelography or MRI may be
necessary to establish the diagnosis. Sedimentation rate, CRP, RA titer,
ANA, and tuberculin tests may be necessary.
» READ BOOK EXCERPT ONLINE »
Source: Differential Diagnosis in Primary Care, 2007
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