infectious module

The Study of Pediatric Infectious Diseases

Why is there a need to know pediatric infectious diseases? We live in a germ filled world. Microbes of infinite variety and complexity colonize our body surfaces and orifices.

Infectious diseases will continue to plague human beings as long as they live in the world we know.

Infectious problems cut across every discipline and subdiscipline of medicine.

What is the responsibility of a physician in relation to treating infectious diseases? The task of the physician is to meet these challenges with confidence borne of increased understanding of the principles of microbiology and immunology and of how these principles are essential to rational decision-making in the clinical areas. Causes of 105 million deaths among children

The Diagnostic Process

It is important to make the anatomic syndrome diagnosis before trying to determine the specific etiologic agent

Clinical diagnosis is an intellectual process in analyzing a patients disease

o A judgment that begins when the patient is first seen; observed signs and symptoms and ends when the diagnosis cannot be refined further

Steps in Diagnosis

History and physical examination o The experienced clinician forms a hypothesis or

tentative diagnosis from the given history o The physical examination can be completed in a

brief period relative to the disease suspected

Working or presumptive diagnosis o Basis for laboratory exams and therapy

Approach to Diagnosis by Symptoms and Signs

Fever of unknown origin

Fever and seizures

Fever and lymphadenopathy

Fever and abdominal pain

Fever and diarrhea

Fever and hepatosplenomegaly

Fever and limp

Fever and neutropenia

Fever and petechiae General Approach to the Child with Possible Infection

A. Detailed history and PE is essential a. History:

Present illness, significant medical history, travel and animal contact, medications, unusual food ingestions and risk of infection with HIV (e.g., IVDU, remote history of blood transfusion, unprotected sexual intercourse)

b. Comprehensive physical examination: Special attention to general appearances,

rashes, skin manifestations of endocarditis, hepatosplenomegaly, evidence of joint effusion, lymph node enlargement

B. Use of the laboratory: Pathogens identified through:

a. Direct methods Cultures of bacteria and viruses Microbiologic stains, including:

Gram stain

Ziehl-Neelsen stain (AFB)

Silver stain (fungal elements)

Wright stain (stool WBCs) Fluorescent antibody-antigen staining for

HSV1 & 2, VZV, RSV, Influenza A and B, parainfluenza

Direct observation including wet mount for fungal elements, dark-field microscopy for T. pallidum

PCR b. Indirect methods

Intradermal skin testing for Mycobacterium tuberculosis and Coccidioides immitis

Antibody testing for viruses: EBV, CMV, VZV, HIV; Toxoplasma gondii, Bartonella henselae and Mycoplasma pneumoniae

c. Nonspecific laboratory indications of infection typically include elevation of acute-phase reactants: CRP and ESR

Fever and Fever of Unknown Origin

Fever

Elevation of body temperature to above normal (37.4C orally or 38C rectally)

Challenge o To establish the causative agent distinguish viral

from bacterial disease o Identify the site of a localized infection

Temperature Variability

Individual to individuals

Diurnal variation in temperature o Circadian rhythm

Oral, axillary or rectal temperatures

Responses among children and adults

Physiological and pathologic states causing fever Physiologic Fever States

Digestion

Exercise

Ovulation

Pregnancy

Warm environment

Emotion Pathologic Causes

Infection

Inflammation (e.g., connective tissue disease)

Neoplasms

Vaccines

Dehydration Common Causes of Fever

Minor Illnesses Major Illnesses

URTI Viral exanthema Gastroenteritis

Bacterial meningitis UTI Pneumonia Malaria

Mechanisms of a Protective Effect of Fever

Enhanced neutrophil migration

Increased production of antibacterial substances by neutrophils

Increased production of interferon

Increased antiviral and antitumor activity of interferon

Increased T-cell proliferation

Decreased growth of microorganisms in iron-poor environment

Extreme Hyperpyrexia (>41C) and Hypothermia

Extreme Pyrexia Hypothermia

Central fevers (neoplastic, trauma, or infection)

Drug fever Heat stroke HIV Malignant hyperthermia Malignant neuroleptic syndrome

Elderly and the newborn (poikilotherms)

Cold exposure Hypothyroidism Overwhelming infection Sepsis in CRF Overzealous treatment

with antipyretics

Pathogenesis of Fever

2 - Pediatrics 2 1st semester || AY 2012-2013 [email protected]

Fever Patterns

Intermittent exaggerated circadian rhythm that includes a period of normal temperature on most days

o High spikes with return to normal

Remitting persistent and varies by more than 0.5C for >24 hours (like intermittent but never returns to normal)

Sustained persistent and does not vary more than 0.5C for >24 hours (like remittent but with less marked swings of temperature)

Relapsing febrile periods that are separated by intervals of normal temperature

o Tertian 1st and 3rd days (P. vivax) o Quartan 1st and 4th days (P. malariae)

Spectrum of Fever Syndromes

Fever without localizing signs

Fever of short duration associated with infection

Recurrent and prolonged fever associated with infection

Fever with a rash

Fever in association with a chronic disease

Fever associated with a collagen diseases

Fever associated with malignancy

Drug fever

Factitious fever

Hospital-acquired Classic Working Definition

Continuous fever of at least 3 weeks duration with daily temperature elevation above 38.3C and remaining undiagnosed after 1 week of intensive study in the hospital

Working Definition (Pediatric)

Fever >38C persisting as a predominant feature for more than 7-10 days in a child in whom a careful, thorough history and physical examination and preliminary laboratory data fail to establish a diagnosis

Fever of Unknown Origin in:

Infectious Causes Noninfectious Causes

Common Mastoiditis (chronic); Sinusitis Salmonellosis Subdiaphragmatic abscess Cytomegalovirus, EBV, Hepatitis viruses Tuberculosis Malaria VLM

Common Leukemia Lymphoma JRA SLE Periodic fever

Uncommon Perinephric abscess Pyelonephritis Psittacosis

Uncommon Polyarteritis nodosa Neuroblastoma Serum sickness

Rare Disseminated Histoplasmosis Toxoplasmosis SBE Leptospirosis

Rare Pancreatitis Drug fever

Etiology

1. Infectious causes 40-50% 2. Collagen-vascular 10-20%

Juvenile rheumatoid arthritis 10% SLE 3% HSP 1% Vasculitis 1%

3. Malignancies/Neoplasms 5-10% Occult solid tumors (neuroblastoma,

Wilms tumor, retinoblastoma) Hematologic tumors

(leukemia, lymphoma, Hodgkins) 4. Miscellaneous 10-15%

Factitious fever Metabolic (drug fever, milk allergy,

dehydrated diabetes insipidus) Genetic (familial Mediterranean fever,

Caffeys disease, hypothalamic dysfunction, hemoglobinopathy crisis)

5. Unknown/undiagnosed 20-30%

What is the Eventual Etiology of FUO in Children?

No. of Cases % of Cases

Infection Respiratory Others

198 102 96

44.4 22.9 21.7

Collagen disease 57 12.8

Inflammatory bowel disease 7 1.6

Neoplasm 25 5.6

No diagnosis 48 10.7

Resolved 56 12.6

Miscellaneous 54 12.1

Infectious

Most frequent o Typhoid fever, malaria, disseminated/miliary TB,

UTI, hidden (cryptic) abscesses, septicemia

Typhoid fever o Stepladder pattern (sustained, progressive) o Fever will not be shorter than five days to a week o Faget sign pulse-fever disproportion

Differential Diagnosis Salmonella Infection (Typhoid Fever)

Seriously and obviously ill with no apparent cause

Abdominal tenderness

Shock

Confusion

Child with sickle-cell disease

Osteomyelitis/arthritis infant

Anemia associated with malaria Malaria

Residence in an endemic area

Blood film positive

Severe anemia

Enlarged spleen

Jaundice Miliary (Disseminated) Tuberculosis

Weight loss

Anorexia, night sweats

Systemic upset

Enlarged liver and/or spleen

Cough

Tuberculin test positive or negative

Sterile pyuria

X-ray shows very widespread small discrete shadows in both lung fields

Sequel of hematogenous dissemination of the organism, which may develop in the post-primary phase or in patients with long-standing latent infection

Also encountered in patients with immunosuppression Pyelonephritis

CVA or suprapubic tenderness

Crying on passing urine

Passing urine more frequently than usual

Incontinence in previously continent child

White blood cells and/or bacteria in urine on microscopy Abscess

Fever with no obvious focus of infection (deep abscesses)

Local tenderness or pain

Fluctuant mass

Specific signs depend on site subphrenic, psoas, lung, renal, retroperitoneal

Follows surgical operations or manipulation/ umbilical catheterization

Septicemia

Seriously and obviously ill, highly-febrile child with no focus of infection

Purpura, petechiae

Shock or hypothermia in a young infant

(+) blood cultures Adage FUO is more likely to be caused by an unusual presentation of a common disorder than a common manifestation of a rare disorder. 3 - Pediatrics 2 1st semester || AY 2012-2013 [email protected]

Evaluation History

Thorough history essential

Careful description of the fever pattern

Attention to associated findings at the time of fever, including tachycardia, skin warmth, and diaphoresis

Exposure to ill contacts

Animal exposure

Travel history (recent and remote)

Dietary history (raw meat/fish ingestion; unpasteurized milk; pica)

Family history (genetic-ethnic background) History of Exposures

Ill persons TB, salmonellosis, viral

Animals Zoonosis, bartonellosis (cat scratch disease), leptospirosis, toxoplasmosis

Travel Malaria, fungi, others

Food Trichinosis

Soil VLM, toxoplasmosis

Drugs Drug fever (antibiotics)

Insects Rickettsia, malaria, others

Clues in the History that may Localize the Infection

Sore throat Strep tonsillitis

Cough, rusty sputum Lobar pneumonia

Severe joint pain/swelling Pyogenic arthritis

Severe pain in head and back of the neck with stiffness

Meningitis

Severe pain in a bone Osteomyelitis

Tender liver Amebic liver abscess Viral hepatitis

Ill-defined subcutaneous inflammation Cellulitis, pyomyositis

Bloody diarrhea Shigella, Campylobacter

Chronic Diseases Complications

Congenital heart diseases Bacterial endocarditis

Cyanotic heart disease Cerebral abscess

Rheumatic fever Bacterial endocarditis Recurrence of RF

Shunted hydrocephalus Shunt infection Ventriculitis, septicemia

Chronic renal disease Urinary tract infection

Congenital or acquired immunodeficiency

Opportunistic organisms, fungi, parasites

Recent surgery Concealed abscesses

Physical Examination

Complete, detailed, thorough and diligent

Repeated frequently. Constant reassessment for specific focal signs can pick up growing tumors/masses/abscesses, changing murmurs or early jaundice

Look for a focus of infection or findings to suggest an occult infectious process; findings suggesting a non-infectious disease

Temperature Chart

Document genuine fever

Clues often overlooked or their significance not appreciated o Review by someone without prior knowledge of

previous finding simportant

Discern fever pattern Approach to the Diagnosis

Exclude factitious fever

Observation of fever in the hospital for 48 hours without antipyretics and observing the pattern

Laboratory studies should be organized towards the most likely diagnosis after complete history and physical examination

Laboratory

The most broadly-based, highest-yield, and most cost-effective testing is done first, and the lowest-yield, most esoteric testing is done last if no diagnosis is made despite persistence of symptoms

Directed toward the most likely diagnostic studies Laboratory Data and Ancillary Procedures

Preliminary o CBC with differential count, platelet count o ESR o Aerobic and anaerobic blood cultures o Urinalysis and urine culture o Chest x-ray film o Tuberculin test o Serologic testing useful in salmonellosis,

brucellosis, tularemia, rickettsial infections o Any other tests indicated by the history or physical

findings

Analyze all data How helpful are CT scans and nuclear medicine studies to determine diagnosis?

Minimally o In prospective study of 109 patients with FUO,

scanning procedures have very low utility in the absence of clinical findings that suggested a localized process

o Bone marrow examination had little value when hematologic abnormalities were lacking in the peripheral blood

Treatment

Stop all medications

Therapeutic (empirical) trials o Suspected disseminated TB o Systemic JRA o Malaria o Rheumatic fever o Culture-negative endocarditis

Diagnosed conditions treat accordingly

Pallor

Jaundice

Rashes/purpura

Mucocutaneous manifestations of systemic diseases

Murmurs or changing murmurs

Abdominal masses or tenderness

Hepatomegaly

Splenomegaly

Lymphadenopathy

Scalp

Eyes

Fundi

Ear drums

Nose

Throat

Gums

Teeth

Sinuses

Bones

Joints

Muscles

External genitalia, pelvic organs

Urine


Gram-Positive Organisms Causing Pyogenic and other Infections

1. Staphylococcus species

a. S. aureus b. S. epidermidis

2. Streptococcus a. S. pneumonia (Pneumococcus) b. Group A Streptococcus (S. pyogenes)

Staphylocccus species

Aerobic cocci that grow in pair or clusters

Either coagulase-positive (S. aureus) or coagulase-negative (S. epidermidis, S. saprophyticus, S. haemolyticus)

Part of the normal flora of humans Pathogenesis

Disease may result from tissue invasion or injury caused by various toxins and enzymes produced by the organisms

Virulent factors o Loose polysaccharide capsule (slime layer) o Coagulase (clumping factor) o Protein A o Catalase, Panton-Valentine leukocidin (PVL),

hemolysins o Penicillinase or -lactamase o Exotoxins ( Exfoliatin A and B) o Enterotoxins (A, B, C1 , C 2 , D, E) o Toxic shock syndrome toxin-1 (TSST-1)

Staphylococcus aureus

The most common cause of pyogenic infections of the skin and soft tissue

o Impetigo, furuncle (boils), cellulitis, abscess, lymphadenitis, paronychia, omphalitis, and wound infection

o Bacteremia osteomyelitis, suppurative arthritis, deep abscesses, pneumonia, empyema, endocarditis, pyomyositis and pericarditis

Toxin-mediated diseases o Food poisoning o Staphylococcal scarlet fever o Staphylococcal skin scalded syndrome (SSSS) o Toxic shock syndrome (TSS)

Clinical Manifestations

The signs and symptoms vary with the location of the infection, which is most commonly the skin but may be any tissue

Skin infections are more prevalent among person living in low socioeconomic circumstances and particularly those in tropical climates

Staphylococcus epidermidis (Coagulase-Negative Staphylococci) (CONS)

Cause infections in patients with indwelling foreign devices intravenous catheters, hemodialysis shunts and grafts, CSF shunts, peritoneal dialysis catheters, prosthetic cardiac valves and prosthetic joints.

Common cause of nosocomial neonatal infection Direct Invasion: Infections Originating from Hair Follicles

Folliculitis Furunculosis

Carbuncle Furunculosis

Impetigo contagiosa

Honey-colored crusts Impetigo Contagiosa and Impetigo Bullosa

Impetigo contagiosa o The classic lesion begin as erythematous papules in

traumatized areas. They quickly evolve into honey-colored crusted plaques with surrounding erythema

o GAS and S. aureus are the chief causative agents

Impetigo bullosa o Exclusively staphylococcal in origin o The characteristic lesion are caused by

epidermolytic toxin

Impetigo contagiosa Impetigo bullosa

Other Staphylococcal Localized Skin Infections

Abscess Cellulitis

Staphylococcal Pneumonia

A. 5 year old child with S. aureus pneumonia initially demonstrated consolidation of the right middle and lower zone.

B. Seven days later, multiple lucent areas are noted as pneumatoceles develop.

C. Two weeks later, significant resolution is evident, with a rather thick-walled pneumatocele persisting in the right midzone associated with significant residual pleural thickening.


Toxin Mediated Disease: Staphylococcal Scalded Skin Syndrome (Ritter disease)

Occurs predominantly in infants and children < 5yr of age

The onset of the rash may be preceded by a prodrome of malaise, fever, and irritability associated with exquisite tenderness of the skin or the appearance of generalized erythema may be abrupt without preceding symptoms.

The erythematous skin may rapidly acquire wrinkled appearance and sterile, flaccid blisters and erosions develop

Circumoral erythema or radial crusting and fissuring around the eyes, mouth, and nose (sunburst pattern)

Areas of epidermis may separate in response to gentle shear force (Nikolsky sign)

Caused by phage group 2 staphylococci, strains 71 and 55

Sunburst pattern

Management of Staphylococcal Infection

Appropriate antibiotics o Oral cloxacillin o Parenteral oxacillin, Cefazolin, vancomycin

[MRSA]+ clindamycin

Incision and drainage

Other supportive measures (toxin-mediated) o fluid replacement o Application of emollient

Streptococccus pneumoniae (Pneumococcus)

Gram positive, lancet-shaped polysaccharide encapsulated diplococcus

Encapsulated strains cause most serious disease in humans (otitis media, life threatening pneumonia, bacteremia, and meningitis)

Capsular polysaccharides impede phagocytosis

Virulence is related in part to capsular size

Invasive strains 4, 6B, 9V,14, 18C, 19F & 23F

Most healthy individuals carry various S. pneumoniae serotypes in their upper respiratory tract (>90% of children 6 mo and 5 yr)

Children 100 serotypes

Types 1, 12, 28, 4, 3, and 2 the most common causes of uncomplicated streptococcal pharyngitis

M types associated with pharyngitis rarely cause skin infections

M types associated with skin infections rarely cause pharyngitis

Pharyngeal strains (M type 12) is associated with glomerulonephritis, while others are associated with rheumatic fever

More of the skin strains (M types 49, 55, 57 and 60) nephritogenic

Produces a large variety of enzymes and toxins (Streptococcal pyrogenic exotoxins A, B, and C)

Common cause of infections of the upper respiratory tract (pharyngitis) and the skin ( impetigo, pyoderma) in children

Also cause distinct clinical entities (scarlet fever and erysipelas), as well as toxic shock syndrome and necrotizing fasciitis

Causes potentially serious nonsuppurative complications: rheumatic fever and acute glomerulonephritis

Pathogenesis: Direct invasion and toxin mediation

Diagnosis: Throat swab culture or rapid antigen detection test

Non-specific pharyngotonsillitis

Highly suggestive of group A -streptococcal infection: palatal petechiae 6 - Pediatrics 2 1st semester || AY 2012-2013 [email protected]

Scarlet Fever

Toxin-mediated disease

Rash appears within 24-48 hours after onset of symptoms

Begins around the neck and spread over the trunk and extremities

It is a diffuse, finely papular, erythematous eruption producing a bright red discoloration of the skin, which blanches on pressure.

More intense along the creases of the elbows, axillae, and groin

The skin has a goose-pimple appearance and feels rough

The face is usually spared, although the cheeks may be erythematous with circumoral pallor

After 3-4 days, the rash begins to fade and is followed by desquamation

The tongue is usually coated and the papillae are swollen (strawberry tongue)

White strawberry tongue Red strawberry tongue Treatment of Streptococcal Infection

Non-invasive: Penicillin

Invasive: Penicillin + Clindamycin Debridement

An Overview of Mucocutaneous Symptom Complex

An exanthem is a skin eruption occurring as an integral part of an infectious disease. The corresponding changes in the mucous membranes is an enanthem. Accurate diagnosis is not always possible on preliminary examination judgment should be deferred until the rash develops. Classification

Maculopapular eruption

Vesiculobullous or vesiculopustular

Petechial or purpuric eruption Measles

Conjunctivitis with photophobia

Kopliks spots graying white dots usually as small as grains of sand, with slight, reddish areola

Distribution of rash o Starts behind the ears along the hairline, face the

spreads downward over the body o More confluent on the upper part, discrete on the

lower part

Brownish discoloration and branny desquamation Rubella (German Measles)

Distribution of rashes are similar to measles but they are discrete and not associated with desquamation

o Rash starts from the trunk and spreads to the neck, face and proximal extremities

Forchheimer spots red spots are often seen on the palate Congenital Rubella Syndrome

Congenital defects occur in >80% of infants infected in the first trimester and virtually no defects are identified in infants infected after the first 16 weeks of gestation

Infants infected in the first trimester are more likely to have multiple congenital defects, whereas those infants infected after 11-12 weeks of gestation are more likely to have only deafness or retinopathy

Clinical Findings in Congenital Rubella Syndrome

General: IUGR, hepatosplenomegaly, chemical evidence of hepatitis

CNS: Mental retardation, behavioral disorders, hypotonia, seizures, CSF protein

Cardiac: PDA, peripheral and valvular pulmonary stenosis, aortic stenosis, VSD

Ocular: Cataracts, salt and pepper retinopathy, corneal clouding, glaucoma

Orthopedic: Radiolucencies in long bones

Hematologic: Transient thrombocytopenia with purpura

Dermatologic: Blueberry muffin spots, dermatoglyphic

Endocrine: Diabetes in 2nd or 3rd decase Prevention

Active immunization (15 months, 4-6 years)

Passive immunization for exposed pregnant woman o Gamma-globulin (.55 mL/kg)

Enteroviral Exanthem Infectious Mononucleosis

Exudative pharyngitis

Cervical lymphadenopathy

Hoaglands sign lid edema Typical Serologic Findings Related to the Stage of EBV Infection

Stage of Infection Presence of Antibody

Primary VCA IgM or IgG (usually high) EA (usually high), no EBNA

Convalescent or Past VCA IgG EA (low), EBNA

Reactivation VCA IgG (high) EA (high), EBNA


Fever with Vesicular/Bullous and Pustular Rash

Risk Factors for Progressive Varicella

Immunodeficiency

Malignancy

Corticosteroid therapy

Pregnant

Newborns

Adolescents and adults Treatment

Neonatal varicella o VZIG and acyclovir

Herpes zoster o Acyclovir (oral) 20 mg/kg/dose max 800 tid to

shorten the course (optional)

Primary varicella o Option of no treatment in a healthy child, unless

with complications treatment with IV acyclovir at 500 mg/m2 or 10 mg/k/dose every 8 hours for 7 days

Prevention

Varicella vaccine live attenuated vaccine given in 2 doses (12-18 months and at 4-6 years)

Post-exposure prophylaxis options o Varicella vaccine within 3-5 days from exposure o VZIG within 96 hours from exposure (recommended

for immunocompromised children, pregnant women, and exposed newborns)

o Pooled IVIG within 96 hours from exposure Pathogenesis

Viral infection begins at a cutaneous portal of entry such as the oral cavity, genital mucosa, conjunctiva, or breaks in keratinized epithelia

Replicate in the sensory neurons, released in nerve endings and replicate again on the skin

Viremia does not play a role in immunocompetent hosts HSV Encephalitis

Leading cause of non-epidemic, sporadic encephalitis in children and adults

It is an acute necrotizing infection involving the frontal and/or temporal and limbic system.

Beyond the neonatal period, it is almost always caused by HSV-1.

Symptoms are non-specific but focal signs are common. If untreated, it can progress to come and death in 75% of cases.

Non-Polio Enteroviruses

Picornaviridae family

Very common viruses with a worldwide distribution

Produce a broad range of important illnesses

The genus name reflects the importance of the GI tract as a primary site of viral invasion and replication and transmission

Enteroviral Exanthems Maculopapular

Rubelliform Echovirus 9, also 2, 4, 11, 19, 25 (Size 1-3 mm) Coxsackie virus A9

Roseola-like Echovirus 16 (Boston exanthema) (Size 5-15 mm) Echovirus 11, 25 Coxsackie virus B1, B5

Vesicular

Hand, foot Coxsackie virus A16, and mouth also A5, A7, A9, A10, B2, B5

Herpangina Coxsackie virus A22, also A1-A10, A16

Insect bite-like Coxsackie virus A4; crops, last 1-2 weeks

Non-pustule Coxsackie virus, also Echovirus 11, 30 forming

Petechial

Coxsackie virus B, A9; echovirus 9

Problem separating from meningococcemia Hand, Foot and Mouth Disease

Most commonly caused by Coxsackie virus A16

The oropharynx is inflamed and contains scattered vesicles on the tongue, buccal mucosa, posterior pharynx, palate, gingiva and/or lips

Maculopapular/vesicular lesions appear in the hands/fingers, feet. Lesions are tender and are common on the dorsal surfaces but can also occur on the palms and soles.

HFMD caused by Enterovirus 71 is more severe with increased rates of neurologic disease.

Herpangina

Sudden onset of fever, sore throat, dysphagia

Characteristic lesions present on the anterior tonsillar pillars, soft palate, uvula and posterior pharyngeal wall, occasionally posterior buccal mucosa

Discrete vesicles that ulcerate, surrounded by erythematous rings

Resolves in 3-7 days Cutaneous Bacterial Infection Impetigo Contagiosa

Erythematous macules that very rapidly evolve into thin-walled vesicles and pustules

The vesiculopustular stage is brief and following rupture, sticky, heaped-up, honey-colored crusts are formed

Risk factors: insect bites, scabies, cutaneous injuries, and preceding dermatitis serve as portals of entry for the organism, which does not penetrate intact skin

Caused by group A -hemolytic streptococcus or S. aureus

Non-bullous or bullous impetigo o Bullous impetigo often caused by S. aureus, most

often phage group 2

Mainly an infection of infants and young children Dengue Fever/Dengue Hemorrhagic Fever Dengue Virus

Causes dengue and dengue hemorrhagic fever

Transmitted by mosquitos

Has 4 serotypes (DEN-1, 2, 3, 4) Aedes aegypti

Dengue transmitted by infected female mosquito

Primarily a daytime feeder

Lives around human habitation

Lays eggs and produces larvae preferentially in artificial containers

Clinical Characteristics of Dengue Fever

Benign syndrome

Biphasic fever

Headache

Myalgia

Arthralgia

Rash morbilliform, maculopapular

Leukopenia

Lymphadenopathy

Petechiae Dengue Hemorrhagic Fever

Known as Philippine, Thai or Singapore hemorrhagic fever, hemorrhagic dengue, acute infectious thrombocytopenic purpura

Severe disease

Occurs where multiple types of dengue virus are simultaneously or sequentially transmitted

Difference in severity is due to difference in immunologic status

Characterized by: o Thrombocytopenia o Increased capillary permeability o Coagulopathy

Phases of Dengue

Febrile phase. Fluid-like symptoms and dehydration

Critical phase. Cardiovascular compromise to shock from leaky capillaries, thrombocytopenia and coagulopathy

Recovery phase. Reabsorption of fluid, may develop hypervolemia in overly aggressive fluid management.


Suggested Dengue Case Classification and Levels of Severity

Course of Dengue Illness

Immunity

Incubation period is 4-10 days

Primary infection can produce a wide spectrum of disease

Individuals are protected from critical illness with other serotypes following a primary infection for the first 2-3 months but with no long-term cross-protective immunity

Risk Factors that Determine Disease Severity

Secondary infection

Age

Ethnicity

Co-morbid chronic diseases: cardiac, pulmonary

Children in general are less able to compensate with capillary leakage than adults

Severe dengue should be considered if the patient is from an area of dengue risk presenting with fever of 2-7 days plus any of the following features:

There is evidence of plasma leakage, such as: o High or progressively rising hematocrit o Pleural effusions or ascites o Circulatory compromise or shock (tachycardia, cold

and clammy extremities, capillary refill time greater than three seconds, weak or undetectable pulse, narrow pulse pressure or, in late shock, unrecordable blood pressure)

There is significant bleeding

There is an altered level of consciousness (lethargy or restlessness, increasing or intense abdominal pain, jaundice)

There is severe organ impairment (acute liver failure, acute renal failure, encephalopathy or encephalitis, cardiomyopathy) or other unusual manifestations

Hemorrhagic Manifestations of Dengue

Skin hemorrhages: petechiae, purpura, ecchymoses

Gum bleeding

Nose bleeding

Gastrointestinal bleeding: hematemesis, melena, hematochezia

Hematuria

Increased menstrual flow Warning Signs for Dengue Shock Four Criteria for DHF

Fever, or recent history of acute fever

Hemorrhagic manifestations

Low platelet count (100,000/mm3 or less)

Objective evidence of leaky capillaries (excessive capillary permeability)

o Elevated hematocrit (20% or more over baseline) o Low albumin o Pleural or other effusions

Initial Warning Signals

Disappearance of fever

Drop in platelets

Increase in hematocrit When Patients Develop DSS

3-6 days after onset of symptoms Alarm Signals

Severe abdominal pain

Prolonged vomiting

Abrupt change from fever to hypothermia

Change in level of consciousness (irritability or somnolence) Differential Diagnosis

Chickungunya (Africa, India, Southeast Asia)

Onyong-nyon (East Africa)

West Nile fever (Europe, Africa, Middle East, India)

Four arboviral diseases with dengue-like course without rash o Colorado tick o Rift valley o Ross river o Sandfly

Meningococcemia and rickettsial diseases Conditions that Mimic the Febrile Phase of Dengue

Flu-like Influenza, chikungunya, infectious mononucleosis

Fever with Rash Rubella, scarlet fever, meningococcal, drug reactions

Diarrheal diseases Rotavirus, other enteric infections

Infections Acute gastroenteritis, malaria, typhoid, leptospirosis, bacterial sepsis and septic shock

Malignancies Acute leukemia and other malignancies 9 - Pediatrics 2 1st semester || AY 2012-2013 [email protected]

Dengue Hemorrhagic Fever

Complications

Carditis

Encephalitis

Severe pleural effusion

End organ damage in severe shock CNS Management

No hemorrhagic manifestations, patient is well-hydrated home treatment

Hemorrhagic manifestations or hydration borderline consider hospitalization

Warning signs (even without profound shock) or DSS hospitalize

Meningococcal Infections

Caused by N. meningitides

Cell wall has lipid A-containing lipo-oligosaccharides, with endotoxin and covered by polysaccharide capsule

At least 13 serotypes identified

Majority of diseases worldwide are caused by serogroups A, B, C, w 135 and Y

Serogroup B most common in infants

Death usually occurs within 6-18 hours Clinical Manifestations

Spectrum o Occult meningococcal bacteremia

Fever with or without symptoms o Meningitis develops in 58% of cases o Acute meningococcemia

Meningococcemia

Purpuric viral exanthema

Petechial facial rash

Ecchymotic lesions Epidemiology

Endemic disease

Male predominance

Invasive disease is most common among young children

50% occur in 25 cases/100,000 in the 1st 4 months of life

25% in people >30 years Pathogenesis

Acquired via respiratory route

Nasopharyngeal colonization usually asymptomatic (because it produces IgA protease)

Meningococcal pili attach to CD46 proteins that induces microvilli formation and endocytosis of the microbe which gain access to the bloodstream

These interactions lead to the production of proinflammatory cytokines, activation of extrinsic and intrinsic coagulation cascade

Capillary leak, DIC leads to multiple organ failure, septic shock and sometimes death

Heart, CNS, skin, adrenals are all affected

Myocarditis >50% of patients

Diffuse adrenal hemorrhage (Waterhouse-Friderichsen syndrome)

Host Factors

Congenital deficiencies of complement components: properdin, factor D and terminal components

Acquired complement deficiencies: SLE, nephrotic syndrome, hepatic failure

Diagnosis

High index of suspicion

Isolation by culture from sterile sites: blood, CSF, synovial fluid

Gram stain and culture of petecchial or purpuric lesions

Gram stain of buffy coat of spun blood Treatment

Drug of choice: Penicillin G 250,000 to 400,000 u/k/day

Cefotaxime and ceftriaxone alternative treatments

Supportive care fluids, vasopressor support, component transfusions

Complications

Acute complications related to vasculitis, DIC and hypotension

Gangrene, adrenal hemorrhage, endophtalmitis, arthritis, endocarditis, pericarditis, pneumonia, renal infarcts, avascular necrosis of epiphyses

Deafness most frequent neurologic sequelae (5-10% of children with meningitis)

Poor Prognostic Factors

Mortality rate as high as 110%

Hypertension, hypothermia or extreme hyperpyrexia on presentation

Purpura fulminans/ptechiae 55 years

Vaccine is unreliable in

Meningitis

Acute Subacute/Chronic

Acute bacterial meningitis Viral meningitis

TB meningitis Fungal meningitis Partially treated BM

Clinical Presentation

Meningitis produces increased ICP because of cerebral edema, obstruction to flow and absorption of CSF and impairing venous outflow

Newborn early and late onset infection o Initial symptoms are non-specific o Later: fever, seizures, bulging fontanel, shock

Older children fever, irritability, neck stiffness, seizures

Kernigs sign, Brudzinskis sign Acute Purulent Bacterial Meningitis: Main Etiologic Agents

Newborn to 3 months o Group B streptococci o E. coli o L. monocytogenes o Enterococci o S. pneumonia

3 months to 6 years o H. influenzae, Type B o S. pneumonia o N. meningitides

>6 years o N. meningitides o S. pneumonia

Viral Meningitis (Aseptic Meningitis)

Usually accompanying the viral infection

Patient manifests signs of the viral infection, as diarrhea, respiratory, mumps, measles, varicella

CSF is usually normal, or with slight increase in cells or protein

Treatment is supportive as the course itself is self-limiting Diagnosis and Treatment

CSF analysis

Neuroimaging if with focal deficits or non-response to tx

Blood, tissue culture

Treatment: antibiotics, antiviral, Anti-Kochs CSF Findings

Type Appearance WBCS Glucose Proteins

Acute Bacterial

Turbid Increased with PMNs predominating

Low Increased

Viral Clear, colorless Normal or slightly increased

Normal Normal or slightly increased

TB/ Fungal

Xanthochromic Increased with lymphocyte predominating

Low Markedly increased

Lumbar Puncture and CSF Analysis

Opening/closing pressure

Appearance clear, colorless, xanthochromic, bloody, turbid, purulent

White blood cell count and differential

Glucose concentration

Protein concentration

Gram stain, AFB stain, fungal stain

Culture

PCR Treatment (Antibiotics used in the treatment of bacterial meningitis depending on the age of the patient and possible agent) Amikacin Ampicillin Cefotaxime

Ceftriaxone Gentamicin Meropenem

Nafcillin Penicillin G Rifampicin

Tobramycin Vancomycin

Duration of Treatment

For uncomplicated PCN sensitive S. pneumonia meningitidis = 10-14 days

For resistant strep vancomycin

For uncomplicated N. meningitidis, IV PCN for 5-7 days

Uncomplicated H. influenza Type B 7-10 days

Gram (-) meningitis 3rd generation cephalosporin, 3 weeks

Complications 1. Seizures 2. Subdural effusions 3. SIADH 4. Prolonged fever 5. DIC

Sequelae 1. Epilepsy 2. Learning disability 3. Motor deficit 4. Visual/hearing

impairment TB Meningitis Three Stages

1. Prodromal fever, headache, irritability 2. Neurologic signs meningeal signs, decreased level of

sensorium 3. Coma, irregular respiration, rigidity, opisthonus

Diagnosis

Clinical: subacute course, (+) TB exposure, (+) tuberculin test

CSF: ground glass appearance with tendency to coagulate, increased WBC with lymphocytosis, extrememly high protein, low sugar

Acid fast staining (+), PCR, ELISA or latex agglutination antigen Treatment

Quadruple anti-TB regimen (HRZ(S/E) 2 mos, HR 10 mos)

Steroids

Treat complications metabolic

Manage increased ICP, hydrocephalus Encephalitis

Usually viral 1. Herpes simplex virus. Presents with signs of increased ICP,

infection and deterioration in consciousness. Tx: acyclovir. 2. Dengue encephalopathy/encephalitis. 3. Subacute sclerosing panencephalitis (SSPE). Subacute and

degenerative disease of the entire brain. Symptoms: behavioral and personality changes, myoclonic jerks, decrease in cognitive function.

Clinical Features

Subtle changes in behavior

Stage 1. Mild symptoms, fever, headache, irritability.

Stage 2. Myoclonus, jerks, but consciousness retained.

Stage 3. Involuntary movements disappear, rigidity, decreased sensorium.

Stage 4. Critical stage with breathing and circulatory problems and death.

SSPE

Diagnosis Treatment

Clinical course (+) measles antibody in the CSF Characteristic EEG findings

No treatment Antiviral drugs under investigation Supportive care

Pseudotumor Cerebri

Condition characterized by increased ICP, normal CSF cell count and protein, normal ventricular size documented by MRI

Causes: metabolic, steroid therapy, hypervitaminosis A, obesity, intake of tetracycline, among others

Clinical features: headache, diplopia, papilledema

Diagnosis: CT, MRI, lumbar tap, CSF analysis

Treatment: determination of the underlying cause, decreased ICP, specific treatment


Pediatric Neurology: Seizures in Children Rosalinda Q. de Sagun October 4, 2007

** Notes in red are from whoever owned the handout I photocopied. Thank you! :3 Seizures

- Refers to excessive neuronal discharge with change in motor activity or behavior (but not always motor manifestation

- Not a diagnosis but a SYMPTOM of an underlying CNS disorder Convulsions

- Refers more to motor attacks Partial Seizures

- Classification depends on site and size of focus

- Focal lesions in brain - From one side/part of brain

A. Simple partial seizures

- Maintained consciousness; may verbalize during the seizure

- Motor (Jacksonian marchfinger, hand, arm, shoulder, face), sensory (numbness in one area), autonomic, psychic

- Pins and needles somatosensory - No automatism

- Often referred to as auras which may consist of an abnormal sensation (e.g., smells, flashing lights) & experimental phenomena (e.g., dj vu)

- Presence of auras always suggests a focal onset of seizure

- If seizure is restricted to a small area in the motor cortex, there is focal clonic activity

B. Complex partial seizures

- Also known as temporal lobe seizures (no longer used) & psychomotor seizures

- With impairment of consciousness (usually starts at prolonged blank stares; confused, prolonged dream-like state)

- Most often behavioral manifestations (violent, disoriented, talking nonsense)

- Involves association fibers

- Temporal & partial cortex lesions - Parietal, frontal, temporal, etc. can also present as this

- With automatism (common feature in children and infants develop after LOC)

- May begin with a simple partial seizure; when the seizure activity spreads, there may be impaired consciousness leading to a complex partial seizure

- Interictal EEG - (+) aura

- May remember start and end of seizure

C. Partial seizures with secondary generalization

- Spreading of the epileptiform discharge during CPS

- Simple or complex evolving to GTC Generalized Seizures

- Due to a diffuse lesion in the brain

- Both hemispheres - Usually from thalamus

- Always with loss of consciousness

A. Absence seizures

- Attacks of fixed blank stares (sometimes with automatisms)

- Always with loss of consciousness - Typical (usually very short duration; no longer than 30 seconds)

or atypical, only in seconds therefore person does not fall on the ground

- With automatic movements such as grimacing - Preschool & early school age renders to have poor academic

performance

- Can occur 20x a days - Diagnosis: EEG2-3 cycles/sec + manifestations =

typical/atypical, EEG not characteristic

- (-) aura - (-) post-ictal

- Hyperventilation for 3 minutes can activated absence seizures - Generalized 3-4 Hz slow spike and wave discharges

B. Tonic clonic

- Grand mal seizure - e.g. Petit mal/Benign febrile seizure (most benign)

- Most dramatic eyes roll upward/back, entire body musculature undergoes tonic contractions, rapidly become cyanotic in association with apnea

C. Tonic

- Extension

D. Clonic - To and fro movement; seizure

E. Myoclonic

- Sudden jerky movements shock like contractions - Difficult to treat; use 1 or 2 anticonvulsants

- Can be a seizure or not

- May be a presenting symptom of a hereditary inborn error of metabolism/ metabolic disease

- Poor prognosis (hard to treat & with underlying abnormality) Infantile Spasm

Severe epileptic syndrome (lifetime)

Very brief; (-) impairment of consciousness

F. Atonic (Astatic) - drop attack prone to injury - Sudden loss of muscle tone, sudden drop down

- Must be differentiated from syncopal attacks - With no risks or predisposing factors

G. Infantile spasms

- Salams seizure like saluting

- Jerky movements

- Attacks are myoclonic; spasm is flexion/bending - Very poor prognosis & difficult to treat

- May be seen in babies with previous asphyxia - Part of the West syndrome

H. Unclassified seizures

- Neonatal seizures rowing movement, grimacing, apnea - Subtle seizures of the newborn

Notes: Automatism alimentary including lip smacking, chewing, swallowing, excessive salivation (infants) semi-purposeful, incoordinated & unplanned gestrural automatisms like picking & pulling at clothing (older children)

Seizure-like Events

A. Night terrors

- Sleep disorder - Wakes up in the middle of the night, does not recognize

parents, does not know what is happening, does not remember anything the next morning

- Related to stress during the day - In contrast with nightmares in which case you remember

your dreams

- Like seizures seizures usually occurs during sleep - Usually seen in school-age children

B. Breath-holding spells

- infants cry holds breath becomes cyanotic (inadequate H20)

- difficult to manage

- check blood Hgb, if low give Fe - do not give anticonvulsants

C. Syncopal attacks

- Usually in adolescence

- Related to stress, heat & environment; Autonomics

D. Shuddering attacks - gigil

E. Pseudoseizures

- adolescents, psychogenic

F. GERD Note: To differentiate : EEG 12 - Pediatrics 2

Causes of Seizures

Non-neurologic Neurologic

Metabolic disorders Electrolyte imbalance (Na, Mg, Ca) Hypoglycemia (esp. newborn) Hypoxia Fever (benign febrile seizure) Systemic infections (UTI, Roseola infantum) Toxins Drug-related (INH low Vitamin B6 pyridoxine)

Tumors CNS malformations Vascular disorders Idiopathic epilepsy CNS infections

*Non-neurologic is easier to confirm Epilepsy

- Recurrent episodes of afebrile seizures - >2 unprovoked seizures occur at an interval >24 hours

- First attack of unprovoked seizures may not result into epilepsy - Type depends on the predominant seizure type e.g. grandmal, petit

mal Status Epilepticus

- Continuous seizures lasting longer than 30 minutes or serial seizures wherein between each seizure, there is no return of consciousness

- A medical emergency case

- Prognosis depends on how case was managed - Subtypes:

- Febrile seizures most common - Idiopathic status epilepticus e.g. patient with menignits

suddenly have seizures

- Symptomatic status epilepticus (tumor) result of an underlying neurologic disorder

- Can be caused by sudden discontinuation of anticonvulsants (most common cause)

- Give circulatory support - Medications:

- Diazepam: short acting; halt seizure - Phenytoin: expensive

- Phenobarbital: can have behavioral manifestations

- Valproate: myoclonic seizures - Phenobarbital coma: for anesthesia

Benign Febrile Seizure

- Temperature >38.4C, evidence of causative disease (CNS infection, metabolic abnormality)

- Children >1 month of age

- Simple: 15minutes in duration - May need investigation to rule out epilepsy

- With focal manifestations

- Increase risk for later epilepsy with the ff characteristics: - Presence of atypical features of seizure or postictal period

- (+) family history of epilepsy - Initial febrile seizure

B. Surgical

- for epilepsy - to cure intractable seizures unresponsive to anticonvulsants

- Vagus nerve stimulation - pacemaker

C. Ketogenic diet

- for epilepsy

- restrict quantity of CHO and CHON and most calories provided as fat

- e.g. Ketocal milk for epileptic patients; only for intractable patients

- must monitor acid-base balance Prophylaxis

- Controversial & prolonged prophylaxis is no longer recommended

- Anti-epileptic drugs (e.g., Phenytoin, Carbamazepine) have no effect gum swelling, behavioral changes

- Phenobarbital is effective but can decrease cognitive functioning

- Na Valproate is effective but there is an increased risk of fatal Valproate-induced hepatotoxicity (highest in 18 months

Complex first febrile seizures

Persistent lethargy

Strongly recommended for children on prior antibiotic therapy Evaluation

History exact description

PE, neuro exam

Age of onset

Precipitating events: prenatal/postnatal insults to the brain

Occurrences of prior seizures (non-convulsive)

Classify the seizure

Family history of seizure most idiopathic are genetic PE

Head size, dysmorphic features

Port-wine stain on face

Trauma

Increased ICP

Metabolic disorders r/t feeding Lab tests (no routine lab tests, to r/o provoked seizures)

Serum glucose determination

Electrolytes

Drug screens

BUN and creatinine

Thyroid function test Diagnosis

Usually clinical

EEG

Neuroimaging

Videotelemetry o Extended EEG (4 hours)

Management

If clearly metabolic, EEG is unnecessary

Treatment with antiepileptic drugs may be needed to control seizures until the underlying pathology responsible for acute encephalopathy is corrected

o 2 weeks seizure free

EEG

To classify the seizures

Provide additional clues in making an etiologic diagnosis

(N) EEG is of limited value and does not rule out that seizure episode has occurred (interictal normal EEG) SSPE periodic lateralized epileptic discharges

To differentiate paroxysmal events

Generalized vs. partial

(+) abnormality o 10-40% absent epileptic o 1-5% present non-epileptic

(may be a genetic variant carrier) Epilepsy

0-4 years old, >70 y/o (bimodal

Pediatric primary (idiopathic)

Older secondary Manifestations

NB hypoxia, metabolic, birth trauma

1-5 febrile seizures, intracranial infection

5-13 genetic epilepsies Neuroimaging

Partial onset (especially adult)

Progressive neurologic disease loss of milestones

Intractable seizures

Seizures increase in frequency and intensity despite adequate treatment

MRI > CT in sensitivity for structural epileptogenic foci Other ILAE Dx Scheme

Syndromic o Predominant seizure type o Age of onset

Infantile Spasm (West Syndrome)

Age-specific

3-12 months, peak 4-7 months

Infantile spasm, MR, hypsarrythmia on EEG

Brief but recurrent spasm (50-100x/d)

Flexor, extensor/mixed

Associated with perinatal injury Lennox-Gastaut Syndrome

Continuum of West

Seizure disorder, MR, atypical pattern on EEG (slower)

Seizure types are variable

Tonic more frequent

Resistant to therapy Benign Rolandic Epilepsy

3-13 years old, peak 9-10

Males > females

More frequent 2-3 hours (p-?) sleep

Grunting, facial twitching secondary generalized (bed wet?) (focal)

EEG: characteristic cortico-temporal spikes

Affected children otherwise normal

Complete remission 15-16 years old Childhood Absence

6-7 years old

Female > male

Simple (blank stare) or complex (automatism/motor component)

Increased Risk for Occurrence in Febrile Seizures

Complex febrile seizures

Family history

Seizures in Children: An Overview

** Additional notes from Panda Manilas photos.

Seizure. An abnormal excessive neuronal discharge arising from the brain, capable of causing alteration in function and/or behavior.

Convulsion. A type of seizure with a motor component.

Epilepsy. Recurrent unprovoked seizures (operational definition more than two.)

Diagnosis of Epilepsies

Everyone is entitled to a diagnosis for prognosis and management to be specific and precise.

The diagnostic label epilepsy is unsatisfactory for both physician and patient because epilepsy is not a single disease entity.

Conditions that Mimic Seizures

Breath-holding spells

Benign paroxysmal vertigo

Night terrors

Syncope

Shuddering attacks

Paroxysmal torticollis

Rage attacks

Masturbation

Hereditary chin trembling

Narcolepsy/cataplexy

Paroxysmal kinesigenic choreoathetosis

Pseudoseizures Absence Seizures

Blank stare beginning and ending abruptly and lasting only a few seconds

Rapid blinking

Chewing

Child is unaware of seizure

Learning difficulties are a possibility

What to do: o No first aid required o If first event, get medical evaluation

Infantile Spasms

Can occur between 6 months and 2 years of age

Appear in clusters of quick, sudden movements

Often mistaken for colic

Most often occur in relation to waking and sleeping times

What to do: o No first aid is needed o Observe duration of clusters o Talk to doctor

Atonic Seizures

Sudden collapsing and falling down

Atonic seizures come in clusters

In less than one minute, child usually regains consciousness and can stand and walk again

Often mistaken for clumsiness

What to do: o Keep child safe during the event o No first aid required o Get medical evaluation

Uses of EEG

Differential diagnosis for other paroxysmal events

Differentiate partial from generalized seizures

Identification of certain epilepsy syndromes

Abnormal epileptiform activities o Absent in 10-40% of epileptic patients o Present in 1-5% of non-epileptic people

Abnormalities of Tone and Movement in Children

Developmental Delay

Delayed acquisition of milestones expected for chronological age

Important to distinguish from progressive neurological disorders, which manifest as loss of previously acquired skills

Delays can involve any developmental parameter/s: motor, language, psychosocial

UMN LMN

Bulk Minimal atrophy Profound atrophy

Tone Increased; spastic Decreased; flaccid

DTRs Hyperreflexia Decreased/absent

Fasciculations Absent Present/absent

Babinski Present Absent

Sensory deficit May be present May be present

Clinical Clues

1. Central Nervous System. UMN (spasticity, hyperreflexia); may be accompanied by cerebral manifestations (seizures, cognition, language and sensory problems)

2. Peripheral Nervous System. LMN (decreased to absent reflexes, flaccid) Guillain-Barre Syndrome

o Acute, autoimmune, polyradiculoneuropathy affecting the PNS, usually triggered by an acute infectious process

o Exhibits an ascending paralysis noted by weakness in the legs that spreads to the upper limbs and the face, along with complete loss of DTRs

Hypotonia o Low neck muscle tone o Child hangs upside down U with little or no

movement o May be transient only child may become spastic

later o More difficult to teach how to walk o Rag doll sign o Floppy

Disorders of the motor system may be:

1. Acute strokes/vascular, metabolic disorders, infections o Seizures

2. Chronic cerebral palsy (static), congenital CNS lesion, degenerative disorders (progressive)

Cerebral Palsy

2/1000

Most common cause of delay

Laymans term

Referred to a group of disorders characterized by motor disorders (tone, posture, or movement), which are neither progressive nor episodic

o Progressive degenerative disease o Episodic seizures

The brain lesions are static and result from disorders of early brain development, usually insults in the perinatal period

o Most consistent factor anoxia, hypoxia of the newborn

o 40% (

(N) reversal of tone from: Axial hypotonia hypertonia Appendicular hypertonia hypotonia Traction test most sensitive test for hypotonia Clinical Manifestations

1. Delay in development (i.e., poor head control, delays in gross motor or fine motor development)

a. Poor head control (usually achieved by 4 months) b. Delays in gross motor or fine motor development

2. Motor deficit depending on the area of the brain involved and usually the risk factors present

3. Associated developmental disabilities mental retardation, epilepsy, visual, hearing, speech and behavioral abnormalities

** 2, 3 severity is proportional Motor Disorders in CP Three main criteria in classification:

1. Type of motor disorder 2. Topographical distribution 3. Gross motor function

Types of Cerebral Palsy and the Major Causes

Physiologic Topographic Etiologic Functional

Spastic Athetoid Rigid Ataxic Tremor Atonic Mixed Unclassified

Monoplegia Paraplegia Hemiplegia Triplegia Quadriplegia Diplegia Double hemiplegia

Prenatal (e.g., infection, metabolic, anoxia, toxic, genetic, infarction) Perinatal (e.g., anoxia) Postnatal (e.g. toxins, trauma, infection)

Class I no limitation of activity Class II slight to moderate limitation Class III moderate to great limitation Class IV no useful physical activity

Spastic Diplegia Periventricular leukomalacia

Prematurity Ischemia Infection Endocrine/metabolic/genetic

Spastic quadriplegia

PVL/multicystic encephalomalacia Malformations

Hemiplegia Stroke in utero or neonatal

Thrombophilic disorders Infection Genetic Hemorrhagic Infarction

Extrapyramidal/ Athetoid

Pathology in the basal ganglia, putamen, globus pallidus, thalamus

Asphyxia Kernicterus Mitochondrial Genetic/metabolic

Hemiplegia

Arm and leg on one side

Arm bent; hand spastic or floppy, often of little use

Walks on tiptoe or outside of foot on affected side

Other side completely or almost normal Paraplegia, Diplegia

Paraplegia both legs only

Diplegia with slight involvement elsewhere

Upper body usually normal or with very minor signs

Child may develop contractures of ankles and feet Quadriplegia

Both arms and both legs

Arms, head, and mouth may twist strangely when walking

Often have severe brain damage, are never able to walk again

Knees press together

Legs and feet turned inward Notes:

Spastic: seesawing of the legs; increase in tone

Athetoid: too much involuntary movement

Rigid: all throughout movement

Monoplegia: uncommon

Diplegia: both lower extremities

Hemiplegia: Right or left half of body

Quadriplegia: Upper and lower extremities

Jitteriness: observe during movement Child with spastic diplegia tip-toe always

*As long as insult happens in neonatal-perinatal period (4 months AOG to 1 months of life) child with meningitis can have cerebral palsy.

Clinical Manifestations

Movement disorders o Spasticity

UE: flexor spasticity LE: extensor spasticity

o Athetosis o Dystonia abnormal posturing o Rigidity o Ataxia ataxia - incoordination o Mixed motor problems

Associated with a spectrum of developmental disabilities: mental retardation, epilepsy, hearing and visual problems, speech, cognitive and behavioral

Physiological Classification Spastic Hemiplegia

spontaneous movements on the affected side

Arm > leg

Delayed walking until 18-24 months of age

Circumductive gait

Growth arrest in extremities especially if contralateral parietal lobe is abnormal

Spasticity in the affected extremities

Equinovarus deformity (walks on tiptoes)

Ankle clonus + Babinski sign

CT: atrophic cerebral hemisphere with dilated lateral ventricle contralateral to the side of the affected extremities

Spastic Cerebral Palsy

Less commonly the head and shoulders may stiffen forward, or the arms may stiffen straight across the body, with the head pressed back

Spastic Quadriplegic Cerebral Palsy

Head may twist to one side; shoulders, head may press back

Fist grips thumbs; arm: may stiffen straight out, or stiffen bent

Legs: may stiffen with knees pressed together, or turn in

Body may stiffen like a board

Stiffness, with the knees bent or with legs separated, occurs more commonly in the child with spasticity and athetosis combined

Most severe form because of involvement of all four limbs and the high association of mental retardation and seizures

Feeding problems (swallowing difficulty) are common due to supranuclear bulbar palsies

Common neuropathologic findings o PVL, multicystic encephalomalacia

Spastic Diplegic Cerebral Palsy

When you try to stand the child, the legs often stiffen

Bilateral spasticity of legs> arm

If severe, there is excessive adduction of the hips making diaper change difficult

Scissoring posture of lower extremities

PVL: most common neuropathologic finding

Prognosis for normal intelligence is good

Minimal seizure Athetoid Cerebral Palsy

Typical athetoid arm and hand movements may be as a regular shake or as sudden spasms. Uncontrolled movements are often worse when the child is excited or tries to do something.

Poor balance, arm and head movement

Child who learns to walk may do so in a stiff, awkward position, with the knees pulled together and bent. Feet often turn in.

Less common than the spastic type.

Hypotonic infants who do not have UMN signs but later on develop increased variable tone (rigidity) and dystonia and other dyskinesias

Intellect is preserved in many cases

Hypotonic with poor head control and marked head lag

Speech affected due to oropharyngeal muscle involvement

UMN signs (-), no seizures, preserved intellect

Most likely associated with birth asphyxia Ataxic Cerebral Palsy

To keep balance, child walks bent forward with feet wide apart, and takes irregular steps (like sailor on a rough sea, or someone who is drunk.)


Diagnosis

Clinical diagnosis

Neuroimaging will document the extent of the structural pathology, aid in diagnosis and prognostication, and rule out treatable causes and slowly progressive neurological disorders

Thorough history to identify risk factors, developmental assessment, physical and neurological examinations

Hearing and vision screening

EEG if with seizures

If no possible etiology or risk factors for CP, do diagnostic tests o Neuroimaging CT/MRI

Document extent of structural pathology o Metabolic screening o Chromosomal studies

Differential Diagnosis

1. Motor delays from congenital structural malformations 2. Progressive disorders of the brain white matter diseases 3. Muscle disorders myopathies, dystrophies 4. Anterior horn cell disease spinal muscular atrophy (SMA)

Differentials

1. Dysmyelinating/demyelinating Disorders o Abnormal myelin formation as in some metabolic

disorders o Abnormal myelin secondary to brain insults from

infection, trauma, autoimmune o Clinically: white matter involvement, with

progressive neurologic deficits (spasticity, hyperreflexia, hearing and vision may be affected)

2. Spinal Muscular Atrophy o Disorders of the anterior horn cell o Usually progressive o Of three varieties depending on the age of onset of

symptoms Infantile type Wednig-Hoffman disease Intermediate Juvenile Kugelberg Welander disease

o Presents with LMN signs: fasciculations, floppy, areflexic

3. Muscle-Congenital Myopathy 4. Nerve disorders

o Manifestations of lower motor disease, decreased reflexes, tone (e.g., hereditary motor-sensory neuropathy)

Effective management requires:

1. Understanding of the pathophysiology of the disorder 2. Careful assessment of the patients capabilities and limitations 3. Knowledge of available treatment regimens, their applications

and limitations Management (Multidisciplinary)

1. Pediatrician 2. Neurologist: management of seizures, botulinum toxin

injections 3. Rehabilition specialists 4. Physical and occuptational therapists 5. Developmental psychologists 6. Education specialists 7. Orthopedic surgeons 8. Social workers

Autism Spectrum Disorder

Autism is a neurodevelopmental disorder of unknown etiology but with a strong genetic basis

Behavioral phenotype o Qualitative impairment in language/communication o Impaired social interactions and reciprocity o Lack of imaginative play

Signs and Symptoms

No pathognomonic symptoms or behavior

Most will present with: o Impairment in joint attention (use of eye contact

and pointing to share experiences with others), which normally develops at 18 months

o Lack of protoimperative pointing (to get an object of desire)

o Lack of protodeclarative pointing (to share an object of interest/naming)

o Lack of imaginative play

Manifestations

Poor eye contact

Verbal abilities vary: non-verbal to advanced speech

Speech may have odd prosody or intonation, echolalia, pronoun reversal, nonsense rhyming

IQ from MR to superior functioning

Stereotypical/ritualistic behaviors

Marked need for sameness Diagnosis

DSM-IV-criteria for autism

Modified checklist for autism in toddlers (M-CHAT)

Pervasive developmental disorder screening test (PDDST) Treatment

Multidisciplinary

Developmental pediatrician, pediatric neurologist, child psychiatrist

Psychologist

Occupational/speech therapist

Special education teacher (if necessary)

Medications depending on co-morbid conditions Attention Deficit Hyperactivity Disorder

Most common neurobehavioral disorder in childhood

Characterized by (DSM IV) o Inattention o Poor impulse control o Motor overactivity/restlessness

Symptoms should be present for more than 6 months in at least 2 settings are significantly affects social, academic or occupational functioning

Etiology

Multifactorial

Genetic susceptibility

Maternal complications during pregnancy

Maternal smoking and alcohol intake during pregnancy

Abnormal brain structures

Psychosocial family stressors exacerbate and/or contribute to the symptoms

Pathogenesis

Smaller prefrontal cortex and basal ganglia with 5-10% less blood flow in these areas.

o Rich in dopamine receptors dopamine hypothesis (disturbances in dopamine system are related to the onset of ADHD)

Diagnosis

Clinical interview and history o Fulfills criteria o Family history of ADHD o Family discord, situational stress

Behavior rating scales (e.g., Conners rating scale) help establish the magnitude and pervasiveness of symptoms and can be used for monitoring improvement with intervention

Treatment

Psychosocial treatments

Behaviorally oriented treatments

Medications: methylphenidate and atomoxetine Prognosis

Persists throughout the life span

Reduction in hyperactive behavior with age

Other symptoms: impulsivity, disorganization and inattention become prominent affecting relationships and occupational functioning

High risk for risk-taking behaviors (substance abuse) and psychiatric disorders

Notes in purple: Transcribed by: Fred Monteverde Notes from: Emy Onishi Cecile Ong Denise Zaballero Notes in red: whoever the notes on my photocopy came from. Thank you!

Fred Monteverde Emy Onishi Cecile Ong Mitzel Mata Regina Luz Section C 2009!


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