This document discusses the approach to evaluating children presenting with developmental regression. It defines developmental regression as the loss of developmental milestones previously attained, indicating a progressive nervous system disease. The evaluation involves a detailed history, developmental assessment, neurological exam, and targeted investigations to identify underlying genetic, metabolic, or acquired etiologies and guide management. A multidisciplinary approach is emphasized to address developmental delays, seizures, contractures, feeding issues, and provide genetic counseling.

1. APPROACH TO
MILESTONE REGRESSION
DR. PIYUSH OJHA
DM RESIDENT
DEPARTMENT OF NEUROLOGY
GOVT MEDICAL COLLEGE, KOTA

2. DEVELOPMENTAL REGRESSION
• Delayed achievement of developmental milestones is one of
the most common problems evaluated by child neurologists.
• Two important questions :
– Is developmental delay restricted to specific areas, or is it
global?
– Is development delayed or regressing?
• Loss of developmental milestones previously attained usually
indicates a progressive disease of the nervous system.

3. • The Denver Developmental Screening Test - an efficient and
reliable method for assessing development.
• Rapidly assesses 4 different components of development:
• Personal- Social
• Fine motor adaptive
• Language and
• Gross motor.

5. • A progressive deterioration of neurological functions - loss of
speech, vision, hearing or locomotion ,often associated with
seizure, feeding and intellectual impairment.
• Neuroregressive / Neurodegenerative Disorders - a group of
heterogeneous diseases which results from specific genetic,
biochemical defect, chronic viral infection and toxic
substances.
• May involves both the gray matter and white matter

6. Normal Development
Regression
Illness/trauma

7. “PSEUDO-REGRESSION”
• Increasing spasticity
• New-onset movement disorder
• New-onset seizures
• Worsening of previous seizures/ NCSE
• Severe malnutrition
• Systemic illness
• Progressive hydrocephalus
• Parental misperception of attained milestones
• Side effects of drugs
• Emotional deprivation
• Emotional problems: depression

8. APPROACH TO A CHILD WITH
MILESTONE REGRESSION

9. IMPORTANT CONSIDERATION
• Regression AND NOT Delay ????
• Age above 2 Years OR Less than 2 Years ???
• Is only the Central nervous system involved, or are other
organs involved?
– Other organ involvement suggests lysosomal, peroxisomal,
and mitochondrial disorders.

10. IMPORTANT CONSIDERATIONS
• Are the clinical features referable only to the central nervous
system or to both the central and peripheral nervous
systems?
– Nerve or muscle involvement suggests mainly lysosomal
and mitochondrial disorders.
• Does the disease affect primarily the gray matter or the white
matter?
– Early features of
• Gray matter disease - personality change, seizures, and
dementia/cognitive decline.
• White matter disease - Focal neurological deficits, spasticity,
and blindness.
– Whether the process begins in the gray matter or white matter,
eventually clinical features of dysfunction develop in both.

11. Fenichel’s Clinical Pediatric Neurology 7th edition

12. Fenichel’s Clinical Pediatric Neurology 7th edition

13. Fenichel’s Clinical Pediatric Neurology 7th edition

14. Differentiating
features
White matter
disorders
Gray matter
disorders
Age of onset Usually late (childhood) Usually early (infancy)
Head size May have
megalenchepaly
Usually microcepaly
Seizures Late , rare Early, severe
Cognitive functions Initially normal Progressive dementia
Peripheral neuropathy Early demyelination Late, axonal loss
Spasticity Early, severe Later, progressive
Reflexes Absent(neuropathy) or
exaggerated(long tracts)
Normal or exaggerated

15. Differentiating
features
White matter
disorders
Gray matter
disorders
Cerebellar signs Early, prominent late
Fundal examination May show optic atrophy Retinal degeneration
EEG Diffuse delta slowing Epileptic form discharges
EMG Slowed nerve
conduction velocity
Usually normal
Evoked potentials
(VEP, ABR)
Prolonged or absent Usually normal
ERG Normal Abnormal

16. Inherited Acquired
Both
White
matter
Gray
matter Metabolic
Infections

17. ACQUIRED CAUSES
Infections
 SSPE
 Progressive Rubella
Syndrome
 Toxoplasma (8% cases)
 Chronic HIV infection
Metabolic
 Chronic lead poisoning
 Hypothyroidism
 Vit B-12 & E deficiency

18. INHERITED CAUSES
• Gray matter involvement:
A. Gray matter involvement with visceromegaly
– GM1 Gangliosides-Infantile , generalized , juvenile
– Sandholf disease
– Niemann pick Disease
– MPS
– Gaucher disease
– Sialidosis

19. B. Gray matter diseases involvement without visceromegaly
– Tay Sach disease
– Rett Syndrome
– Neuronal ceroid lipofuscinosis
– Menke’s kinky hair disease

20. WHITE MATTER INVOLVEMENT
Leukodystrophies
– Metachromatic leukodystrophy
– Krabbe disease
– Adrenoleukodystrophy
– Alexander disease

21. OBJECTIVE OF EVALUATION
• Confirmation of Developmental regression
• Categorization of domains involved
• Identification of possible underlying etiology
• Referral to appropriate rehabilitation services
• Management of associated co-morbidities
• Multidisciplinary approach
• Counselling
Shevell, 1998

22. • Birth history:
– Term/preterm
– Postnatal complications
• Meningitis
• Head trauma
• kernicterus

23. • Developmental history:
– Detailed development history- decide whether there is
delayed development milestones or regression of
milestones
• Family history:
– Family history of neurological disorder
– Early or unexplained death
– Nature of the neurological manifestations should be
clarified
• H/o of consanguinity - ethnic heritage
– Origin from same village
– Same last names

24. • Gestational history
– Prior pregnancies/ abortions/ Early postnatal deaths
– Adverse perinatal events – hypoxia/hypoglycemia
– Delivery details
– Apgar, birth weight
– Duration of hospital stay/ difficulties in Nutrition
– Possible neonatal encephalopathy : seizures, feeding
difficulty, obtundation

25. • Developmental history
– First domain of concern
– Timing of milestones
– Loss/regression
– Current skill level in domains
– Degree of independence in daily activities
– Scholastic performance; special needs
• Coexisting medical problems
• Past medical history; treatment
• Social history
• Access to rehabilitation

26. CLINICAL EXAMINATION
• General physical examination
– Dysmorphism: Mitochondrial disorders, Neonatal adrenal
leukodystrophy ,coarse facial features (MPS)
– Occipito-Frontal Circumference –
• Microcepaly (gray matter disease)
• Megalenchepaly – certain white mater
disorder(Cannavan & Alexander)
– Jaundice
– Enlarged tongue

27. • Skin & hair ( Hartnup Diseases-pellagra like skin rash, Menkes
disease-kinky hair)
• Examination of the spine- for associated complications
(scoliosis)
• Contractures of joints
• Systemic examination:
– Hepatosplenomegaly
– Chest deformity
– Cardiomyopathy

28. NEUROLOGICAL EXAMINATION
• Higher mental function, signs of raised ICP
• Speech, memory
• Cranial nerves
• Motor system:
– Tone
– Deep tendon reflexes
• Sensory loss /neuropathy
• Abnormal /involuntary movements
• Gait

29. EYE EXAMINATION
• Optic atrophy (white matter- due to demyelination)
• Retinal degeneration (gray matter)- as the retinal receptors
are neuronal cells): Cherry red spot, retinitis pigmentosa
• Cataracts
• Telengiectasias
• K.F ring

30. INVESTIGATIONS
• To identify the underlying diagnosis & associated
complications
• CBC- pancytopenia, vacuolated lymphocytes, acanthocytes
• ABG - metabolic acidosis(organic acidopathies, urea cycle
defects, mitochondrial encephalopathies)
• Electrolytes (Anion gap), for adrenal insufficiency
(adrenoleukodystrophy)
• Ammonia level, LFTs, RFTs

31. • Special tests:
– Lactate & pyruvate levels, Lysosomal enzyme level
– WBCs, Fibroblast enzyme level
– Wilson’s disease-serum ceruloplasmin level, serum copper
– Amino acids
– Urinary organic acids

32. • Urine
– Reducing substances, Organic acids,24 hr (MPS)
• Imaging
– Skull & Vertebrae, Long bones
– CT/MRI
• Biopsy
– Skin, Bone marrow, nerve, brain
• Diagnosis
– Important for genetic counseling
• Outcome - Prognosis poor

33. BELIEVE IN HISTORY AND EXAMINATION !!!
(GLOBAL DEVELOPMENTAL DELAY AND REGRESSION)

34. MANAGEMENT
• Directed towards the treatment of the underlying disorder,
other associated features and complications
• Supportive : The treatable complications :
• feeding difficulties, Gastoresophageal reflux
• spasticity, drooling
• skeletal deformities, and recurrent chest infections
• epilepsy, sleep disorder, behavioral symptoms
• A multidisciplinary approach (Pediatrics, neurology, genetics,
orthopedics, physiotherapy, and occupational therapy).

35. SPECIFIC TREATMENT
Neurodegenerative
disorders
Specific treatment modality
Krabbe leukodystrophy Bone marrow transplantation
Metachromatic leukodystrophy Bone marrow transplantation
Adrenoleukodystrophy Glyceryl trioleate and trierucate,steroids for
adrenal insufficiency, diet low in VLCFA, bone
marrow transplantation
Mucopolysaccharidosis Bone marrow transplantation,
recombinant human α-L-iduronidase
Menkes kinky hair syndrome Copper sulfate

36. Neurodegenerative
disorders
Specific treatment modality
Mitochondrial encephalopathies Nicotinamide, riboflavin,
dichloroacetate, L-carnitine, CoQ10
Wilson disease D- penicillamine, trietine, zinc acetate,
liver transplantation
Refsum disease Reduction of phytanic acid intake
Lesch-Nyhan disease Allopurinol
Fabry’s Disease Recombinant human α galactosidase A

37. Guanidinoacetate Methyltransferase Deficiency
• Rare but treatable disorder
• Amidinotransferase converts glycine to guanidinoacetate and
guanidinoacetate methyltransferase converts
guanidinoacetate to creatine.
• Autosomal recessive inheritance (19p13.3)
• Affected children appear normal at birth and may develop
normally during infancy.
• By the end of the first year, development fails to progress and
hypotonia is noted.
• Regression of development follows and is associated with
dyskinesias, dystonia, and myoclonic jerks.

38. • MRI -marked demyelination
• MR Spectroscopy - creatine depletion and guanidinoacetate
phosphate accumulation.
• Management - Early oral administration of creatine
monohydrate significantly prevents and reverses all
symptoms, and late treatment provides some reduction of
abnormal movements.

39. • Main defect - almost complete deficiency of the enzyme
cystathionine- b -synthase (Picker and Levy, 2006).
• Two variants –
– B 6 - responsive &
– B 6 –nonresponsive
• AR inheritance
HOMOCYSTINURIA

40. HOMOCYSTINURIA
• Affected individuals appear normal at birth.
• Neurological features - mild to moderate MR, ectopia lentis,
and cerebral thromboembolism.
• Developmental delay ( 50% cases) and intelligence declines
progressively with age in untreated children.
• Most eventually function in the mildly retarded range.
• Intelligence generally higher in B 6 –responsive cases.
• Thromboembolism - first clue to the diagnosis in 15% cases.
• The presence of either thromboembolism or lens dislocation
strongly suggests homocystinuria.

41. HOMOCYSTINURIA
• Diagnosis - increased concentrations of plasma homocystine,
total homocysteine, and methionine; increased concentration
of urine homocystine; and reduced cystathionine b-synthase
enzyme activity.
• Molecular genetic diagnosis available.
• Management. Challenge all patients with Pyridoxine (vitamin
B 6 ) before starting treatment.
• IF responsive – Pyridoxine (200 mg/day)
• IF Not responsive - still receive doses of 100 to 200 mg/day.
• All patients - protein-restricted diet.
• Treatment with betaine, 5 to 10 g/day in two divided doses,
provides an alternate remethylation pathway to convert
excess homocysteine to methionine.

42.  Autosomal Recessive
 Galactosylceramide b -galactosidase deficiency
 Myelin loss & presence of globoid bodies in white matter
 EARLY ONSET VARIANT :
 Symptom appear by 6 months
◦ Irritability Vomiting
◦ Bouts of hyperpyrexia Progressive hypertonicity
Startle Myoclonus, Seizures UMN signs with areflexia
 Within 2 to 4 months, the infant is in a permanent position of
opisthotonos, and all previously achieved milestones are lost.
 Blindness occurs, and before 1 year, 90% of these infants are
either dead or in a chronic vegetative state.

43.  LATE ONSET VARIANT :
 Neurological deterioration usually begins at 2-6 yrs.
 May start as early as the second year or as late as
adolescence.
 Major features - Mental regression, cortical blindness, and
generalized or unilateral spasticity.
 Initial feature may be progressive spasticity rather than
dementia.
 Unlike the infantile form, peripheral neuropathy is not a
feature of the juvenile form.
 Progressive worsening -> a vegetative state.

44.  Investigations
◦ MRI – diffuse demyelination
◦ Leukocyte & Skin fibroblast enzyme level
◦ CSF Protein : Early variety – elevated
Late Onset Variety - Normal
◦ Motor NCV: Markedly prolonged latencies
 Management - Hematopoietic stem cell transplantation slows
the course of disease in children with infantile-onset Krabbe
disease diagnosed before symptom onset.
 Neurological manifestations may reverse.

45. TAY SACHS DISEASE
• N-acetyl- b -hexosaminidase deficiency
• Intralysosomal storage of the glycosphingolipid GM 2
ganglioside.
• Complete deficiency - Tay-Sachs disease
• CNS – the only affected organ.
• Partial deficiencies cause the juvenile and adult forms of GM 2
gangliosidosis.

46. TAY SACHS DISEASE
• Typical initial symptom - between 3-6 months - an abnormal
startle reaction (Moro reflex) to noise or light.
• Motor regression begins between 4 and 6 months of age.
• The infant comes to medical attention because of either
delayed achievement of motor milestones or loss of
milestones previously attained.
• Cherry-red spot on macula present in almost every patient
(NOT Pathognomic)
• By 1 year - infant is severely retarded, unresponsive, and
spastic.
• 2nd year - the head enlarges and seizures develop.
• Most children die by 5 years of age.

47. JUVENILE VARIANT :-
• Often begins with ataxia and incoordination between 2 and 10
years of age.
• Speech, life skills, and cognition decline.
• Spasticity and seizures present by end of 1st decade
• Loss of vision occurs much later than infantile form.
• Cherry-red spot not a consistent finding.
• Optic atrophy and retinitis pigmentosa occur late.
• A vegetative state with decerebrate rigidity by 10-15 years.
• Followed by death, usually due to infection.
• Sometimes may follow a aggressive course, culminating in
death in 2 to 4 years.

48. TAY SACHS DISEASE
• Diagnosis - Suspect the diagnosis in any Jewish child with
psychomotor retardation and a cherry-red spot on the
macula.
• Demonstration of absent to nearly absent b -hexosaminidase
A enzymatic activity in the serum or white blood cells or
Fibroblast.
• Mutation analysis identifies the carrier state.
• Management - Treatment is supportive.

49.  Commonest
 AR inheritance (Chr 1q21)
 Deficiency of Glucocerebrosidase
 5 types
◦ Type 1 – Perinatal lethal form – spares Brain
◦ Type 2 – onset < 2 years, rapidly progressive course
by 2-4 years
◦ Type 3 – onset > 2 years, slowly progressive course with
longer survival
◦ Type 4
◦ Type 5 – cardiovascular form

50. Gaucher disease type 2 – symptom onset usually < 6 months
• Initial features – motor regression and cranial nerve
dysfunction.
• Children are first hypotonic and then spastic.
• Head retraction - an early and characteristic sign - probably
due to meningeal irritation.
• Difficulties in sucking and swallowing, trismus, and
oculomotor palsies are typical.
• Mental deterioration is rapid , seizures uncommon.
• Splenomegaly >> hepatomegaly, jaundice not expected.
• Hypersplenism - anemia, thrombocytopenia, and leukopenia.
• Death usually occurs during the first year and always by the
second.

51. Gaucher disease type 3 –
• Age of onset – early childhood to adulthood
• Hepatosplenomegaly usually precedes neurological
deterioration.
• MC neurological manifestations - seizures and mental
regression (mild memory loss to severe dementia)
• Myoclonus and myoclonic seizures present in many patients.
• Combination of spasticity, ataxia, and cranial nerve
dysfunction may be present.
• Vertical oculomotor apraxia, as described in Niemann-Pick
disease, may occur in late-onset Gaucher disease as well.

52. • Diagnosis –
– Assay of acid b –glucosylceramidase enzyme activity in
peripheral blood leukocytes or hepatocytes
– Gaucher cells in bone marrow - pathognomic
• Management - Symptomatic treatment includes partial or
total splenectomy, blood transfusion, analgesics and
supplemental treatment such as oral bisphosphonates for
severe osteopenia.
• Type 3 disease - may benefit from bone marrow
transplantation to correct the metabolic defect.
• Enzyme replacement therapy, using Imiglucerase (CEREZYME),
is effective in reversing the hematological and liver/spleen
involvement BUT NOT NEUROLOGICAL SYMPTOMS.

53. Bone marrow smear showing Gaucher cell. The cytoplasm has a fibrillary and
striated appearance with nuclei small and eccentric in location MGG ×100

54.  Absence of variety of lysosomal hydrolases involved in the
catabolism of dermatan sulfate, heparan sulfate, or keratin
sulfate.
 Defective degradation of Mucopolysacharides
 7 types recognised – Type 1,2,3 and 7 affect nervous system
 Multisystem involvement
 Coarse facial features , Dwarfism , Kyphoscoliosis
 Macrocephaly, with or without communicating hydrocephalus
 Hepatosplenomegaly , Cardiovascular abnormalities
 Hearing loss , contractures

55.  Type 1 & 3 – onset in infancy
 Type 2 & 7 – onset after > 2 yrs of normal development
 Type 2 – Hunter syndrome (X linked inheritance)- deficient
Iduronate Sulfatase
 Diagnosis : -
◦ Mucopolysacchariduria with equal excretion of dermatan
sulfate and heparan sulfate
◦ enzyme deficiency in cultured fibroblasts or serum.
 Enzyme replacement therapy with Aldurazyme, licensed for
treatment of the non–CNS manifestations of MPS I, improves
liver size, growth, joint mobility, breathing, and sleep apnea.

56.  Onset is usually after age 2 with slow progression.
 AR inheritance
 Early development is normal.
 Mean age of onset = 3 years
 Cerebellar ataxia or dystonia is initial feature
 Apraxia of vertical gaze and cognitive difficulties follow (6yrs)
 Vertical gaze apraxia always suggests Niemann-Pick disease
type C.
 Relentless progressive neurological degeneration.
 Dementia, seizures, and spasticity cause severe disability
during the 2nd decade.
 Impaired cholesterol esterification and positive filipin staining
in cultured fibroblasts confirm the diagnosis.

57.  Inherited white matter disease
 Defect in myelin synthesis
 Involves brain, spinal cord and peripheral nerves.
 Classic dysmyelinating disorders are
Adrenoleukodystrophy, Metachromatic Leucodystrophy,
Krabbe's disease

58.  Autosomal Recessive
 Arylsulfatase A deficiency deficiency
 Infantile (50-60% cases) and Juvenile variety(20-30%)
 Age at onset within a family usually similar.
 All individuals eventually lose motor and intellectual
functions.
 The disease course - 3 to 10 or more years in the late-
infantile-onset form and as long as 20 years or more in the
juvenile- and adult-onset forms.
 Death – due to pneumonia or other infection.
 Treatment is mainly supportive .

59.  Onset in late infancy
• Hypotonia initially
• Peripheral neuropathy
• Dysarthria
• Optic atrophy
• Mental regression
• Decorticate posture
finally
 Expected life span ~ 3.5
years after onset of
symptoms but can be as
long > 10 years
Onset at 5-10 yr
• Deterioration in school
performance
• Alteration in personality
• Incontinence
• Seizures
• Incoordination, Dysarthria
• Gait disturbances
• Spasticity
• No peripheral neuropathy
• Slow progression
• Spastic quadriplegia
eventually
•Death usually during 2nd decade.

60.  Life-threatening disorder
 deficiency of a peroxisomal acyl coenzyme A synthetase.
 occurring in males, affects white matter & adrenal gland.
 Very long chain fatty acids accumulate in the cells & tissues
causing myelin sheath damage as well as dysfunction of the
adrenal gland.
 X-linked form is the commonest
 Diagnosis is made by estimation of very long-chain fatty acids
in plasma

61.  AR
 Storage of auto fluorescent hydrophobic material in
lysosomes of neurons & other tissue
 3 subtypes – Infantile / Late infantile / Juvenile
 Symptoms/ Signs
◦ Myoclonic jerks , seizures (5-9 years)
◦ Visual symptoms
◦ Cerebellar ataxia
◦ Cognitive decline (5-9 years)
◦ Pigmentary abnormalities in retina (4-5 years)

62.  Mean age of survival = 10 yrs
 Investigation
 Skin biopsy:
◦ Ultra structural abnormalities- characteristic Finger-print
bodies
 Cortical biopsy:
◦ Distended neurons – characteristic Finger-print bodies
◦ Staining for ceroid & lipofuscinosis
 Treatment – symptomatic

63.  Zellweger syndrome : dysmorphic features &severe
psychomotor retardation, sensory neuronal deafness,
peripheral neuropathy & hepatocellular degeneration.
 Diagnosed by demonstrating the elevated very long chain
fatty acids, pipecolic acid and bile and derivatives.

64.  Females affected only
 Mutations in the gene encoding methyl-CpG-binding protein-2,
located on chromosome Xq28
 Normal during 1st year
 Initial features - deceleration of head growth leading to
microcephaly, lack of interest in the environment & hypotonia.
 Followed by rapid developmental regression characterized by
loss of language skills, gait ataxia, seizures, and autistic
behavior.
 Characteristic feature - loss of purposeful hand movements
before the age of 3.
 Stereotyped activity develops that looks like hand wringing or
washing.

65.  Repetitive blows to the face – another stereotyped hand
movement.
 Following the initial rapid progression - continued slower
progression of neurological deterioration.
 Spastic paraparesis and quadriparesis - frequent endpoints.
 Dementia is usually severe.
 Stimulation produces an exaggerated stereotyped reaction
consisting of jerking movements of the trunk and limbs with
episodes of disorganized breathing and apnea followed by
hyperpnea.

66.  Seizures - most children before age 3 years.
 After the period of rapid deterioration, the disease becomes
relatively stable, but dystonia may develop later.
 Patients usually survive into early adulthood
 An increased incidence of sudden, unexplained death.
 Diagnosis - Clinical features & molecular genetic testing.
 Management - Supportive.

67. Wilson’s disease
 AR
 Degenerative disease of basal ganglia
 Inborn error of copper metabolism
 Academic deterioration
 Behavioral changes , Dysarthria ,Dysphasia
 Drooling , Dystonia
 K F ring

68. Acquired Immunodeficiency Syndrome Encephalopathy
• Human retroviral disease (Lentivirus subfamily)
• Transplacental or perinatal transmission of HIV from mothers
• Breast-feeding
• The mother may be asymptomatic when the child becomes
infected.
• Evidence of infection is apparent during the first year in 30%
of children born to AIDS-infected mothers.
• Outcome is worse when the onset of symptoms is early, and
the rate of progression in the child relates directly to the
severity of disease in the mother.
• 20% children present with severe symptoms or die in infancy.

69. Acquired Immunodeficiency Syndrome Encephalopathy
• The spectrum of neurological and non-neurological
manifestations in HIV-infected children is somewhat different
from that of adults.
• Hepatosplenomegaly and bone marrow failure, lymphocytic
interstitial pneumonia, chronic diarrhea and failure to thrive,
acquired microcephaly, cerebral vasculopathy, and basal
ganglia calcification occur more frequently in children.
• Opportunistic infections (e.g., cerebral toxoplasmosis,
progressive multifocal leukoencephalopathy) are rare in
infants.

70. Acquired Immunodeficiency Syndrome Encephalopathy
• AIDS encephalopathy - subacute or indolent
• Not necessarily associated with failure to thrive or
opportunistic infections.
• Onset of encephalopathy may occur from 2 months to 5 years
after exposure to the virus.
• 90 % affected infants show symptoms by 18 months of age.
• Progressive loss of developmental milestones, microcephaly,
dementia, and spasticity characterize the encephalopathy.
• Other features (< 50% cases) - ataxia, pseudobulbar palsy,
involuntary movement disorders, myoclonus, and seizures.
• Death usually occurs a few months after the onset of AIDS
encephalopathy.

71. Acquired Immunodeficiency Syndrome Encephalopathy
• DNA PCR - preferred method for the diagnosis in infants and
children > 18 months of age.
• Combined treatment with zidovudine (azidothymidine),
didanosine, and nevirapine is well tolerated and may have
sustained efficacy against HIV-1.

72.  Form of chronic measles encephalitis
 In a nonimmunized population, the average age at onset is 8
years.
 As a rule, children have experienced natural infection with the
rubeola virus at an early age, half of them before age 2 years.
 First symptoms - Personality change and declining school
performance.
 Personality change - aggressive behavior or withdrawal.

73. • Retinal examination during early stage shows pigmentary
changes in the macula.
• Generalized seizures, usually myoclonic, develop next.
• EEG - characteristic pattern of periodic bursts of spike-wave
complexes (approximately every 5–7 sec) occurring
synchronously with the myoclonic jerk.
• After the onset of seizures, the child shows rapid neurological
deterioration characterized by spasticity, dementia, and
involuntary movements.
• Within 1 to 6 years from the onset of symptoms, the child is in
a chronic vegetative state.

74. • Diagnosis – demonstration of an increased antibody titre,
usually associated with increased g –globulin concentrations,
in the CSF.
• Intraventricular interferon-alfa combined with oral
isoprinosine, 100 mg/kg/day.
• Repeat courses up to six times at 2- to 6-month intervals.

75. THANK YOU

76. REFERENCES
• Bradley’s Neurology in clinical practice 6th edition
• Adams & Victor’s Principles of Neurology 10th edition
• Fenichel’s Clinical Pediatric Neurology 7th edition

77. COST OF VARIOUS TESTS AT DNA LABS INDIA