Hypotonia in Hypotonia in ChildrenChildren

Dr. Mohamed AbunadaDr. Mohamed AbunadaPediatric Neurology DepartmentPediatric Neurology Department

Dr. Al Rantisi Specialized Children Dr. Al Rantisi Specialized Children HospitalHospital

DefinitionDefinition

Muscle tone is defined as resistance to Muscle tone is defined as resistance to passivepassive

movement.movement.

Hypotonia means "Hypotonia means "low tonelow tone," and refers ," and refers to a physiological state in which a muscle to a physiological state in which a muscle has decreased tone, or tension.has decreased tone, or tension.

Hypotonia in Hypotonia in ChildrenChildren The maintenance of normal tone requires intact The maintenance of normal tone requires intact

central and peripheral nervous systems. central and peripheral nervous systems. Hypotonia is a common symptom of neurological Hypotonia is a common symptom of neurological

dysfunction and occurs in diseases of the brain, spinal dysfunction and occurs in diseases of the brain, spinal cord, nerves, and muscles . cord, nerves, and muscles .

One anterior horn cell and all the muscle fibers that it One anterior horn cell and all the muscle fibers that it innervates compose innervates compose a a motor unitmotor unit.. The motor unit The motor unit is the unit of force. Weakness is a symptom of all is the unit of force. Weakness is a symptom of all motor unit disorders. motor unit disorders.

A primary disorder of the anterior horn cell body is a A primary disorder of the anterior horn cell body is a neuronopathyneuronopathy,, a primary disorder of the axon or a primary disorder of the axon or its myelin covering is a its myelin covering is a neuropathyneuropathy,, and a primary and a primary disorder of the muscle fiber is a disorder of the muscle fiber is a myopathymyopathy. In . In infancy and childhood, cerebral disorders far infancy and childhood, cerebral disorders far outnumber motor unit disorders. outnumber motor unit disorders.

Hypotonia in Hypotonia in ChildrenChildren

Classification(Classification( Location) Location) BrainBrain Spinal cordSpinal cord Peripheral nervesPeripheral nerves Neuromuscular TransmissionNeuromuscular Transmission MusclesMuscles Systemic disordersSystemic disorders

Hypotonia in Hypotonia in ChildrenChildren

In supine, In supine, Frog position Their Their heads lag when are held upwhen are held up They They slip through at the shouldersat the shoulders Do Do not standnot stand upright on their legs upright on their legs Form Form inverted U shape shape in ventral suspensionin ventral suspension Lie flatLie flat when in prone positionwhen in prone position..

Signs of Signs of HypotoniaHypotonia

Signs of HypotoniaSigns of Hypotonia

Poor ability to cough and clear airway secretions.Poor ability to cough and clear airway secretions. Poor swallowing abilityPoor swallowing ability Crying character [weak, low pitched]Crying character [weak, low pitched] Paradoxical breathing pattern. Intercostal muscles Paradoxical breathing pattern. Intercostal muscles

paralyzed with intact diaphragm.paralyzed with intact diaphragm.

Signs of HypotoniaSigns of Hypotonia

Ventral suspensionVentral suspensionInverted U positionInverted U position The back hangs over the The back hangs over the

examiner's hand, and the limbs examiner's hand, and the limbs and head hang looselyand head hang loosely

Passive extension of the legsPassive extension of the legs

Pull to sit Pull to sit Head lagHead lag

Signs of HypotoniaSigns of Hypotonia

The same infant in horizontalsuspension. Note the inverted U posture.

Signs of HypotoniaSigns of Hypotonia

A 12-week-old male infant with excessive head-lag A 12-week-old male infant with excessive head-lag evident on ‘evident on ‘pull-to-sitpull-to-sit’. Note the hypotonic posture ’. Note the hypotonic posture

of the legs with external rotation.of the legs with external rotation.

Signs of HypotoniaSigns of Hypotonia

Vertical suspension:Vertical suspension: The legs will be extendedThe legs will be extended Decreased tone of the shoulder girdle allows the infant to slip through the examiner's hands Decreased tone of the shoulder girdle allows the infant to slip through the examiner's hands

Approach to Diagnosis Approach to Diagnosis The first step in diagnosis is to determine whether the The first step in diagnosis is to determine whether the

disease location is in the brain, spine, or motor unit. disease location is in the brain, spine, or motor unit. More than one site may be involved More than one site may be involved The brain and the peripheral nerves are The brain and the peripheral nerves are

concomitantly involved in some lysosomal and concomitantly involved in some lysosomal and mitochondrial disorders. mitochondrial disorders.

Brain and skeletal muscles are abnormal in infants with Brain and skeletal muscles are abnormal in infants with acid maltase deficiency and neonatal myotonic acid maltase deficiency and neonatal myotonic dystrophy.dystrophy.

Newborns with severe hypoxic-ischemic encephalopathy Newborns with severe hypoxic-ischemic encephalopathy may have hypoxic injury to the spinal cord and the brain may have hypoxic injury to the spinal cord and the brain

AssessmentAssessment

Prenatal risk factors:Prenatal risk factors: • • History of drug or teratogen exposureHistory of drug or teratogen exposure • • Presence of polyhydramniosPresence of polyhydramnios • • Maternal diseases (diabetes, epilepsy)Maternal diseases (diabetes, epilepsy) • • Parental ageParental age • • ConsanguinityConsanguinity • • Family history of neuromuscular diseaseFamily history of neuromuscular disease • • Other affected siblingsOther affected siblings

History TakingHistory TakingAny significant family history?Any significant family history?Was the Hypotonia present at birth?Was the Hypotonia present at birth?Pregnancy and delivery historyPregnancy and delivery history

Drug or teratogen exposure Drug or teratogen exposure Decreased fetal movements Decreased fetal movements Abnormal presentation Abnormal presentation Polyhydramnios/ oligohydramniosPolyhydramnios/ oligohydramnios

Apgar scores Apgar scores Resuscitation requirements Resuscitation requirements

Hypotonia in Hypotonia in ChildrenChildrenClues in CEREBRAL HypotoniaClues in CEREBRAL Hypotonia

Cerebral Hypotonia in newborns usually does Cerebral Hypotonia in newborns usually does not pose diagnostic difficulty. The history and not pose diagnostic difficulty. The history and physical examination identify the problem. physical examination identify the problem.

Normal or Brisk reflexesNormal or Brisk reflexes Other abnormal brain functions: delay, Other abnormal brain functions: delay,

seizuresseizures FistingFisting Movement through postural reflexesMovement through postural reflexes Scissoring on vertical suspensionScissoring on vertical suspension Dysmorphic featuresDysmorphic features Extra-cranial organ malformationsExtra-cranial organ malformations

Hypotonia in Hypotonia in ChildrenChildren

Clues in MOTOR UNIT HypotoniaClues in MOTOR UNIT HypotoniaDisorders of the motor unit are not associated Disorders of the motor unit are not associated

with malformations of other organs except for with malformations of other organs except for joint deformities and the mal development of joint deformities and the mal development of bone structures. bone structures.

Absent or Depressed reflexesAbsent or Depressed reflexes Intact brain functionIntact brain function Muscle atrophyMuscle atrophy FasciculationsFasciculations Failure of movement through postural reflexesFailure of movement through postural reflexes No extra-cranial organ malformationsNo extra-cranial organ malformations

ClassificationClassificationHEAD - BRAINHEAD - BRAIN

Hypoxic ischemic EncephalopathyHypoxic ischemic Encephalopathy Hypotonic Cerebral PalsyHypotonic Cerebral Palsy Benign Congenital HypotoniaBenign Congenital Hypotonia Excessive Subarachnoide spaceExcessive Subarachnoide space ArthrogyroposisArthrogyroposis Cerebellar disorders Cerebellar disorders Cortical DysgenesisCortical Dysgenesis

Cerebral dysgenesisCerebral dysgenesis ((Chronic Non progressive Chronic Non progressive

Encephalopathy)Encephalopathy) may be due to known or unknown noxious environmental may be due to known or unknown noxious environmental

agents, chromosomal disorders, or genetic defects. agents, chromosomal disorders, or genetic defects. In the absence of an acute encephalopathy, hypotonia may In the absence of an acute encephalopathy, hypotonia may

be the only symptom at birth or during early infancy. be the only symptom at birth or during early infancy. Hypotonia is usually worse at birth and improves with time. Hypotonia is usually worse at birth and improves with time. Cerebral dysgenesis is suspected when hypotonia is Cerebral dysgenesis is suspected when hypotonia is

associated with malformations in other organs or associated with malformations in other organs or abnormalities in head size and shape. abnormalities in head size and shape.

Magnetic resonance imaging (MRI) of the head is advisable Magnetic resonance imaging (MRI) of the head is advisable when cerebral malformation is suspected.when cerebral malformation is suspected.

The identification of a cerebral malformation provides The identification of a cerebral malformation provides useful information not only for prognosis, but also on the useful information not only for prognosis, but also on the feasibility of aggressive therapy to correct malformations in feasibility of aggressive therapy to correct malformations in other organs.other organs.

Hypotonic cerebral palsyHypotonic cerebral palsy

Many hypotonic children due to causes in Many hypotonic children due to causes in central nervous system are mentally retarded. central nervous system are mentally retarded. In atonic or hypotonic cerebral palsy, reflexes In atonic or hypotonic cerebral palsy, reflexes are brisk in spite of generalized flaccidity. are brisk in spite of generalized flaccidity. Floppy infant due to cerebral causes is Floppy infant due to cerebral causes is associated with lethargy, poor feeding, and associated with lethargy, poor feeding, and lack of alertness, poor Moro’s reflex, and lack of alertness, poor Moro’s reflex, and seizures during the neonatal period.seizures during the neonatal period.

Benign Congenital Benign Congenital Hypotonia Hypotonia

The term The term benign congenital hypotoniabenign congenital hypotonia is is retrospectiveretrospective and refers to infants who are and refers to infants who are hypotonic at birth or shortly thereafter and later hypotonic at birth or shortly thereafter and later have normal tone. have normal tone.

It encompasses many It encompasses many different pathological different pathological processesprocesses that affect the brain, the motor unit, or that affect the brain, the motor unit, or both. both.

Most affected children have cerebral hypotonia. Most affected children have cerebral hypotonia. An increased incidence of mental retardation, An increased incidence of mental retardation,

learning disabilities, and other sequalae of learning disabilities, and other sequalae of cerebral abnormality are evident later in life, cerebral abnormality are evident later in life, despite the recovery of normal muscle tone.despite the recovery of normal muscle tone.

Hypotonia in Hypotonia in ChildrenChildren

SPINAL CORDSPINAL CORD Spinal Cord Injury – Broken NeckSpinal Cord Injury – Broken Neck Spinal Muscular AtrophySpinal Muscular Atrophy

WERDNIG-HOFFMANNWERDNIG-HOFFMANN INFECTIONSINFECTIONS

Enterovirus - POLIOEnterovirus - POLIOTransverse MyelitisTransverse Myelitis

MASS LESIONSMASS LESIONS

Spinal Cord InjurySpinal Cord Injury Injuries in Breech PresentationInjuries in Breech Presentation Injuries to the cervical spinal cord occur almost Injuries to the cervical spinal cord occur almost

exclusively during vaginal delivery; exclusively during vaginal delivery; approximately 75% are associated with breech approximately 75% are associated with breech

presentation andpresentation and 25% with cephalic presentation. 25% with cephalic presentation. Because the injuries are always associated with a Because the injuries are always associated with a

difficult and prolonged delivery, decreased difficult and prolonged delivery, decreased consciousness is common, and hypotonia is falsely consciousness is common, and hypotonia is falsely attributed to asphyxia or cerebral trauma.attributed to asphyxia or cerebral trauma.

Radiographs of the vertebraeRadiographs of the vertebrae show no abnormalities show no abnormalities because bone displacement does not occur. because bone displacement does not occur. MRI of MRI of the spinethe spine shows intraspinal edema and hemorrhage shows intraspinal edema and hemorrhage

Spinal Cord InjurySpinal Cord Injury Injuries in Cephalic PresentationInjuries in Cephalic Presentation Twisting of the neck during midforceps Twisting of the neck during midforceps

rotation causes high cervical cord injuries in rotation causes high cervical cord injuries in cephalic presentation. cephalic presentation.

The trunk fails to rotate with the head. The trunk fails to rotate with the head. The risk is greatest when amniotic fluid is The risk is greatest when amniotic fluid is

absent because of delay from the time of absent because of delay from the time of membrane rupture to the application of membrane rupture to the application of forceps. forceps.

Werdning-Hoffman Werdning-Hoffman SyndromeSyndrome

SMA type 1SMA type 1 Anterior Horn cell (neuronal) Anterior Horn cell (neuronal)

degenerationdegeneration Progressive Weakness: Proximal > DistalProgressive Weakness: Proximal > Distal HypotoniaHypotonia AreflexiaAreflexia Atrophy / FasciculationsAtrophy / Fasciculations Intact Brain DevelopmentIntact Brain Development

SMASMA SMA is the SMA is the second most common second most common

autosomal recessive disease in the US after cystic in the US after cystic fibrosis.fibrosis.

Incidence:Incidence: Type 1: 1 per 10,000 live birthsType 1: 1 per 10,000 live births Types II and III: 1 per 24,000 birthsTypes II and III: 1 per 24,000 births

Worldwide 7.8-10 cases per 100,000 live births Worldwide 7.8-10 cases per 100,000 live births ? M:F predominance or M>F? M:F predominance or M>F No ethnic predominance.No ethnic predominance.

SMASMA The genetic defects associated with SMA The genetic defects associated with SMA

types I-III are localized on chromosome types I-III are localized on chromosome 5q11.2-13.3.5q11.2-13.3.

Mutations in the Mutations in the SMN SMN gene result in a gene result in a loss of function of the SMN protein. loss of function of the SMN protein.

Many classification systems based on Many classification systems based on inheritance, clinical, and genetic criteria. inheritance, clinical, and genetic criteria.

SMA Type 1SMA Type 1 SMA type I,SMA type I, ( (Werdnig-Hoffmann acute infantileWerdnig-Hoffmann acute infantile), ),

occur birth – 6 months (95% by 3 months)occur birth – 6 months (95% by 3 months) Severe, progressiveSevere, progressive muscle weakness and flaccid muscle weakness and flaccid

or reduced muscle tone (hypotonia). or reduced muscle tone (hypotonia). Bulbar dysfunctionBulbar dysfunction includes poor suck ability, includes poor suck ability,

reduced swallowing, and respiratory failure. reduced swallowing, and respiratory failure. Patients have Patients have no involvement of the extraocular no involvement of the extraocular

musclesmuscles, and facial weakness is often minimal or , and facial weakness is often minimal or absent.absent.

They have They have no evidence of cerebral involvementno evidence of cerebral involvement, , and infants appear and infants appear alertalert..

SMA Type 1SMA Type 1 Impaired fetal movementsImpaired fetal movements are observed in 30% are observed in 30%

of casesof cases 60% of infants with SMA type I are floppy 60% of infants with SMA type I are floppy

babies at birth. babies at birth. Prolonged cyanosisProlonged cyanosis may be may be noted noted at delivery. at delivery.

In some instances, the disease can cause In some instances, the disease can cause fulminant weakness in the first few days of life. fulminant weakness in the first few days of life. Such severe weakness and early bulbar Such severe weakness and early bulbar dysfunction -> mean survival of 5.9 months.dysfunction -> mean survival of 5.9 months.

Affected children Affected children never sit or standnever sit or stand.. In In 95% of cases95% of cases, infants , infants diedie from complications from complications

of the disease by of the disease by 18 months18 months. .

SMA Type 2SMA Type 2 SMA type IISMA type II ( (chronic infantile, sitterschronic infantile, sitters) )

usually begin between usually begin between 6 - 18 months6 - 18 months.. Most common form of SMAMost common form of SMA Most common manifestation is Most common manifestation is

developmental motor delaydevelopmental motor delay. Infants with . Infants with SMA type II often have difficulties with SMA type II often have difficulties with sitting independentlysitting independently or or failure to stand by 1 failure to stand by 1 year of age. year of age.

These children may learn to sit but will These children may learn to sit but will never be able to stand or walk.never be able to stand or walk.

SMA Type 2SMA Type 2 An unusual feature of the disease is An unusual feature of the disease is a postural a postural

tremor affecting the fingerstremor affecting the fingers. This is thought to . This is thought to be related to fasciculations in the skeletal be related to fasciculations in the skeletal musclesmuscles

Pseudohypertrophy of the gastrocnemius Pseudohypertrophy of the gastrocnemius muscle, musculoskeletal deformities, and muscle, musculoskeletal deformities, and respiratory failure can occur.respiratory failure can occur.

The lifespan of patients with SMA type II varies The lifespan of patients with SMA type II varies from 2 years to the third decade of life.from 2 years to the third decade of life. Respiratory infections account for most deaths. Respiratory infections account for most deaths.

SMA Type 3SMA Type 3 SMA type III (SMA type III (Kugelberg-Welander, Kugelberg-Welander, chronic juvenile, chronic juvenile,

walkerswalkers)) appear appear 18 months – adult18 months – adult.. Slowly progressive proximal weakness. Most Slowly progressive proximal weakness. Most can can

stand and walkstand and walk but have trouble with motor skills, but have trouble with motor skills, such such as going up and down stairs.as going up and down stairs.

Bulbar dysfunction occurs late in the disease. Bulbar dysfunction occurs late in the disease. Patients may show evidence of Patients may show evidence of pseudohypertrophy.pseudohypertrophy. The disease progresses slowly, and the overall The disease progresses slowly, and the overall

course is mildcourse is mild. Many patients have . Many patients have normal life normal life expectancies. expectancies.

SMASMA Congenital SMA with arthrogryposisCongenital SMA with arthrogryposis

(persistent contracture of joints with fixed (persistent contracture of joints with fixed abnormal posture of the limb) is a rare abnormal posture of the limb) is a rare disorder. Manifestations include disorder. Manifestations include

1.1. severe contracturessevere contractures, , 2.2. curvature of the spinecurvature of the spine, , 3.3. chest deformitychest deformity, , 4.4. respiratory problemsrespiratory problems, , 5.5. an an unusually small jawunusually small jaw, and , and 6.6. drooping upper eyelids. drooping upper eyelids.

Poliovirus InfectionPoliovirus Infection

Small RNA virus : NeurotropicSmall RNA virus : Neurotropic Destroys neurons causing paralysisDestroys neurons causing paralysis Seasonal epidemicsSeasonal epidemics Prodromal illnessProdromal illness Pain --> Asymmetric ParalysisPain --> Asymmetric Paralysis Rare but still occursRare but still occurs vaccine related : 1 in 12 millionvaccine related : 1 in 12 million wild type due to groups refusing to wild type due to groups refusing to

vaccinatevaccinate

MASS LESIONS OF SPINAL MASS LESIONS OF SPINAL CORDCORD

RareRare Intra-Abdominal TumorsIntra-Abdominal Tumors NeuroblastomaNeuroblastoma Early in InfancyEarly in Infancy

PERIPHERAL NERVESPERIPHERAL NERVES

PolyneuropathyPolyneuropathy DysmylinationDysmylination

AUTOIMMUNEAUTOIMMUNECONGENITAL / GENETICCONGENITAL / GENETIC

DysautonomiaDysautonomia

MUSCLESMUSCLESCONGENITAL MYOPATHIESCONGENITAL MYOPATHIES

DYSTROPHINOPATHIESDYSTROPHINOPATHIES DUCHENNE’SDUCHENNE’S BECKER’SBECKER’S

CENTRAL CORECENTRAL COREMYOTUBULARMYOTUBULARNEMALINE RODNEMALINE RODMYOTONIC DYSTOPHYMYOTONIC DYSTOPHY

Infantile MyositisInfantile Myositis

NEUROMUSCULAR NEUROMUSCULAR JUNCTIONJUNCTION

Toxins Toxins BotulismBotulism

MyastheniaMyastheniaCongenitalCongenitalNeonatal transitoryNeonatal transitory

INFANTILE BOTULISMINFANTILE BOTULISM

Infants usually 2 - 26 weeks oldInfants usually 2 - 26 weeks old Clostridium Botulinum --> ExotoxinClostridium Botulinum --> Exotoxin Prevents release of AcetylcholinePrevents release of Acetylcholine Cholinergic Blockade of skeletal muscleCholinergic Blockade of skeletal muscle Source of intestinal colonization usually Source of intestinal colonization usually

unclearunclear Occurs mainly between March & OctoberOccurs mainly between March & October

INFANTILE BOTULISMINFANTILE BOTULISM

Prodrome: poor feeding & Prodrome: poor feeding & constipationconstipation

Progressive bulbar & general Progressive bulbar & general weaknessweakness

Loss of deep tendon reflexesLoss of deep tendon reflexes HypotoniaHypotonia DysphagiaDysphagia Ptosis Ptosis Sluggish dilated pupilsSluggish dilated pupils

INFANTILE INFANTILE MYASTHENIAMYASTHENIA

FAMILIAL-INFANTILEFAMILIAL-INFANTILE Multiple Genetic Defects: AR + Multiple Genetic Defects: AR +

ADAD Pre & Post Synaptic AChR Pre & Post Synaptic AChR

abnormalitiesabnormalities Respiratory or feeding problems Respiratory or feeding problems

at birth at birth CONGENITALCONGENITAL

Usually Bilateral Ptosis & Usually Bilateral Ptosis & OphthalmoplegiaOphthalmoplegia

Multiple Genetic Defects: AR Multiple Genetic Defects: AR NEONATAL-TRANSITORYNEONATAL-TRANSITORY

10 - 15% of myasthenic mothers10 - 15% of myasthenic mothers

Signs of HypotoniaSigns of Hypotonia

Ptosis and external ophthalmoplegia in a floppy weak child. Ptosis and external ophthalmoplegia in a floppy weak child. Suggestive of myasthenia gravis.Suggestive of myasthenia gravis.

TreatmentTreatment

FAMILIAL-INFANTILEFAMILIAL-INFANTILEneostigmine or pyridostigmineneostigmine or pyridostigmine

CONGENITALCONGENITALAnticholinesterases for face, not for eye movementsAnticholinesterases for face, not for eye movements3, 4-Diaminopyridine for some (increases ACh)3, 4-Diaminopyridine for some (increases ACh)

NEONATAL-TRANSITORYNEONATAL-TRANSITORYSevere: exchange transfusionSevere: exchange transfusionMild - mod: 0.1% neostigmine methylsufate IM before feedsMild - mod: 0.1% neostigmine methylsufate IM before feedsor nasogastric tube 10 x parenteral doseor nasogastric tube 10 x parenteral dose

JOINTS & CONNECTIVE TISSUEJOINTS & CONNECTIVE TISSUE

Congenital Joint LaxityCongenital Joint LaxityAchondroplasiaAchondroplasiaMarfan SyndromeMarfan SyndromeEhlers-Danlos SyndromeEhlers-Danlos SyndromeOsteogenesis ImperfectaOsteogenesis Imperfecta

HYPOTONIA and HYPOTONIA and WEAKNESSWEAKNESS

in INFANTS in INFANTSSYSTEMICSYSTEMIC

GENETIC DISORDERSGENETIC DISORDERS INFECTIONINFECTION

SEPSIS SEPSIS INGESTIONSINGESTIONS

LIDOCAINELIDOCAINE

SYSTEMICSYSTEMICGENETIC DISORDERSGENETIC DISORDERS

PRADER-WILLIPRADER-WILLIANGELMAN’S SYNDROMEANGELMAN’S SYNDROMECRI DU CHATCRI DU CHATCEREBRO-HEPATO-RENAL CEREBRO-HEPATO-RENAL SYDROMESYDROME

WILLIAM’S SYNDROMEWILLIAM’S SYNDROMETRISOMY 21TRISOMY 21TRISOMY 13TRISOMY 13

HYPOTONIA and HYPOTONIA and WEAKNESSWEAKNESS

in INFANTS in INFANTS PRADER-WILLI SYNDROMEPRADER-WILLI SYNDROME HypogenitalismHypogenitalism 100% 100% CryptorchidismCryptorchidism 84%84% Decreased Fetal MovementDecreased Fetal Movement 75%75% Congenital Hip DislocationCongenital Hip Dislocation 10%10% ClubfootClubfoot 6% 6% Profound Infantile HypotoniaProfound Infantile Hypotonia Mental RetardationMental Retardation Decreased / Absent DTRsDecreased / Absent DTRs Short StatureShort Stature Obesity / Insatiable AppetiteObesity / Insatiable Appetite

SYSTEMICSYSTEMICMETABOLICMETABOLIC

MITOCHONDRIALMITOCHONDRIALCongenital Lactic ACIDOSISCongenital Lactic ACIDOSISHyperammonemiaHyperammonemiaAMINOACIDURIASAMINOACIDURIAS

NON-KETOTIC NON-KETOTIC HYPERGLYCINEMIAHYPERGLYCINEMIA

Celiac DiseaseCeliac DiseaseAnaemiaAnaemiaFAILURE TO THRIVE (FTT) FAILURE TO THRIVE (FTT)

DIAGNOSTIC STUDIESDIAGNOSTIC STUDIES

HEAD CT, MRI: Brain edema, HEAD CT, MRI: Brain edema, dysgenesis, otherdysgenesis, other

Xray, US, CT: Fracture, MassesXray, US, CT: Fracture, Masses BLOOD:BLOOD: Infection, Metabolic, Genetic Infection, Metabolic, Genetic URINE: Infection, MetabolicURINE: Infection, Metabolic CSF: Infection, MetabolicCSF: Infection, Metabolic Anal Swab: Enterovirus, C. botulinumAnal Swab: Enterovirus, C. botulinum EMG/NCV: SMA, MG, GBSEMG/NCV: SMA, MG, GBS Tensilon Test: MG vs other DxsTensilon Test: MG vs other Dxs

METABOLIC EVALUATIONMETABOLIC EVALUATION

Arterial Blood: Lactate, Pyruvate, ABGArterial Blood: Lactate, Pyruvate, ABG Venous Blood: Ammonia, Chemistries Venous Blood: Ammonia, Chemistries

CBC, CBC, Carnitine profile, Amino AcidsCarnitine profile, Amino Acids

Urine: Organic & Amino AcidsUrine: Organic & Amino Acids CSF: Lactate, Amino Acids CSF: Lactate, Amino Acids

(Glycine) (Glycine) Muscle: It DependsMuscle: It Depends

GENETIC EVALUATIONGENETIC EVALUATION

Consultation with a geneticistConsultation with a geneticist

ManagementManagement

Supportive [respiratory, gastrointestinal]Supportive [respiratory, gastrointestinal] Once the correct diagnosis is confirmed, specific Once the correct diagnosis is confirmed, specific

treatments should be offered if availabletreatments should be offered if available Physiotherapy: Physiotherapy:

mainly preventative to avoid contractures and wasting, but will not increase mainly preventative to avoid contractures and wasting, but will not increase muscle tonemuscle tone

Genetics counseling.Genetics counseling.

PrognosisPrognosis

Currently no known treatment or cure for most causes Currently no known treatment or cure for most causes of hypotonia, and objective manifestations can be life of hypotonia, and objective manifestations can be life long.long.

The outcome in any particular case of hypotonia The outcome in any particular case of hypotonia depends largely on the nature of the underlying disease.depends largely on the nature of the underlying disease.

PrognosisPrognosis

In some cases, muscle tone improves over time, or In some cases, muscle tone improves over time, or the patient may learn mechanisms that enable him the patient may learn mechanisms that enable him to overcome the most disabling aspects of the to overcome the most disabling aspects of the disorder. disorder.

Hypotonia caused by cerebellar dysfunction or Hypotonia caused by cerebellar dysfunction or motor neuron diseases can be progressive and life-motor neuron diseases can be progressive and life-threatening.threatening.

Differential Diagnosis of Infantile HypotoniaCerebral Hypotonia

1. “Benign” congenital hypotonia2. Chromosome disorders

a. Prader-Willi syndromeb. Trisomy

3. Chronic nonprogressive encephalopathya. Cerebral malformationb. Perinatal distressc. Postnatal disorders

4. Peroxisomal disordersa. Cerebrohepatorenal syndrome (Zellweger)b. Neonatal adrenoleukodystrophy

5. Other genetic defectsa. Familial dysautonomia

b. Oculocerebrorenal syndrome (Lowe)6. Other metabolic defectsa. Acid maltase deficiency (see “Metabolic Myopathies”)

b. Infantile GM, gangliosidosis

Differential Diagnosis of Infantile Hypotonia

Spinal Cord Disorders1. Hypoxic-ischemia myelopathy

2. InjuriesSpinal Muscular Atrophies

1. Acute infantile2. Chronic infantile

3. Incontinentia pigmenti4. Infantile Spinal Cord Disorders5. Neurogenic arthrogryposisPolyneuropathies1. Congential hypomyelinating neuropathy

2. Giant axonal neuropathy3. Hereditary motor-sensory neuropathies

Differential Diagnosis of Infantile Hypotonia

Disorders of Neuromuscular Transmission1. Infantile botulism

2. Familial infantile myasthenia3. Transitory myasthenia gravis

Fiber-Type Disproportion Myopathies

1. Central core disease2. Congential fiber-type disproportion myopathy3. Myotublar (centronuclear) myopathy

a. Acuteb. Chronic

4. Nemaline (rod) myopathy

Differential Diagnosis of Infantile Hypotonia

Infantile Myositis

1. Acid maltase deficiency2. Cytochrome-c-oxidase deficiency

3. Carnitine deficiency4. Phosphofructokinase deficiency5. Phosphorylase deficiency

Metabolic Myopathies

Muscular Dystrophies1. Congential muscular dystrophy

a. Cerebroocular dystrophyb. Fukuyama typec. Leukodystrophy

2. Congenital myotonic dystrophy

HYPOTONIA and HYPOTONIA and WEAKNESSWEAKNESS

in INFANTS in INFANTSBIBLIOGRAPHYBIBLIOGRAPHY Fenichel GM, Fenichel GM, Clinical Pediatric Clinical Pediatric

Neurology: A Signs and Symptoms Neurology: A Signs and Symptoms ApproachApproach, 2nd ed.WB Saunders, 2nd ed.WB Saunders

Adams RD, Victor M, Adams RD, Victor M, Principles of Principles of NeurologyNeurology, 4th ed. McGraw-Hill, 4th ed. McGraw-Hill

Menkes JH, Menkes JH, Textbook of Child Textbook of Child NeurologyNeurology, 5th ed.Williams and , 5th ed.Williams and WilkinsWilkins

Oski FA, Oski FA, Principles and Practice of Principles and Practice of PediatricsPediatrics, Lippincott, Lippincott