2. The hallmark of a neurodegenerative disease is
regression and progressive deterioration of neurologic
function with loss of speech, vision, hearing, or
locomotion, often associated with seizures, feeding
difficulties, and impairment of intellect
3. Neuroregression in children is associated
with loss of memory, ability to think, understand and
recognize along with personality changes or distressing
behavior.
Vision loss, hearing loss, tone abnormalities and epilepsy are other
common symptoms. This neurological deterioration is not explainable
by any other concurrent systemic illness.
Neurodegenerative disorders of childhood encompass a large,
heterogeneous group of diseases that result from specific
genetic and biochemical defects, chronic viral infections, and varied
unknown causes.
Continue….
4. As a first step to clinical evaluation, pseudoregression should be excluded in all cases.
Regression can occur without an underlying neurodegenerative process due to poorly
controlled seizures, over-medication with anticonvulsants, intercurrent systemic illness and
secondary neurological problems in a static encephalopathy, e.g. loss of mobility due to
development of joint contracture, seizures, movement disorder, etc. or depression or other
emotional problems especially in older children
Some children may present with progressivemental deterioration, seizures and vision loss.
Yet another group of children, presents with recurrent neurological
deterioration interspersed with apparent recovery (organic
aciduria, mitochondrial disorders, urea cycle disorders, etc.).
•In girls with regression in cognitive spheres starting in infancy, microcephaly and associated
with loss of purposeful hand movements “Rett syndrome” should
be considered.
•Additionally, a possibility of HIV encephalopathy should always be kept in mind and
systematic evaluation for risk factors should be undertaken.
APPROACH TO REGRESSION IN
CHILDREN
5. During infancy delayed milestones are common manifestation of
neuroregressive disorders. Since the child has not gained many
distinctive abilities, the loss of abilities is difficult to quantify or
localize. Commonly, the infant lacks visual interest or socialization has
poor head control and inability to use hands.
Other common symptoms are developmental retardation with severe
hypotonia especially with feeding difficulties and/or vomiting and
failure to thrive.
Many disorders that present in the second year of life are frequently
recognizable by the obvious loss of motor abilities. This may result
from corticospinal, cerebellar, extrapyramidal or peripheral nerve
involvement.
The second year of life is also the age for disorders with gradually
increasing dysmorphism, skeletal abnormalities and cognitive decline
[mucopolysaccharidosis (MpS) and mucolipidosis].
REGRESSION IN 2 YR OLD CHILD
6. FEATURE GRAY MATTER WHITE MATTER
DEMENTIA EARLY LATE
SEIZURE EARLY LATE
PYSCHOLOGICAL SIGNS MAY BE UNCOMMON
BASAL GANGLIA SINGS OFTEN PRESENT ABSENT
RETINITIS PIGMENTOSA MAY BE PRESENT ABSENT
PRIMARY OPTIC ATROPY RARE MAY BE SEEN
PRIMARY NEUROPATHY RARE MAY BE SEEN
IMAGING MRI Cortical atropy,abnormalities
in basal ganglia,cerebellum
Clearly identified the white
matter lesion
ERG and VER Usually abnormal normal
7. AGE AT ONSET (2yrs) CONDITIONS COMMENTS
<2 with hepatomegaly FRUCTOSE INTOLERANCE Vomiting ,hypoglycemia,poor
feeding,failure to
thrive(when given frustose)
GALACTOSEMIA Lethargy,
hypotonia,icterus,cataract,hy
poglycemia(when given
lactose)
Glycogenosis(glycogen
storage disoders)
Hypoglysemia
cardiomegaly(type 2)
Mucopolysaccharridosis
type1 and 2
Coarse facies,stiff joints
Niemann pick disease
,infantile type
Gray matter disease failure to
thrive
Tay sachs disease Seizures,cherry red
spot,edema,coarse facies
Zellweger Hypotonia high forehead flat
8. <2 ,without hepatomegaly Krabbes disease Irritabiliy,extensor
posturing,0ptic atrophy and
blindness
Rett syndrome Girls with decrleration of
head growth,loss of hand
skill,hand writing,impaired
language,skills,gait apraxia
Maple syrup disease Poor feeding
,tremors,myoclonus,opisthot
onos
Phenylketonuria Light
pigmetation,eczema,seizures
Menke kinky hair disease Hypertonia,irritability,seizure,
abnormal hair
Canvan disease Megacephaly white matter
disease
Pelizaeus-Merzbacher
disease
White matter disease
9.
10.
11.
12. NEURODEGENRATIV
E DISODERS
MODE OF
INHERITANCE
BIOCHEMICAL
DEFECT
SPECIMEN FOR
ANALYSIS
Spingolipidosis
GM1 gangliosidosis AR Beta-Galactosidase Serum,leukocytes,ski
n,fibroblast
GM2 gangliosidosis AR
Tay-sachs disease AR Hexosaminidase A Serum,leukocytes,ski
n,fibroblast
Sandoff disease AR Hexosaminidase A
and B
Serum,leukocytes,ski
n,fibroblast
Krabbes AR Galactocerebrosidase Leukocyte skin and
fibroblast
Metachromatic
leukodystrophy
AR Arylsulfatase A Leukocyte skin and
fibroblast
Neuronal ceroid
lipofuscinoses
AR Pamitoyl-protein
thioesterase
EM of skin biopsy
