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Cerebellar involvement in
movement disorders related to
Autism

Hexanto Muhartomo
Pediatric Neurodevelopment Subdivision
Departement of Neurology, Faculty of Medicine
Diponegoro University/Dr.Kariadi Hospital
Semarang

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 AUTISM

• Autism is defined as neurological

disorders characterized by communication
and social interaction disorders and
repetitive behavior, in children less than 30
months old.

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 Introduction
o Leo Kanner 1943
o 11 children :
– Communication disorders
– Repetitive behavior
– Social isolation

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 Epidemiology
• Prevalence tends to increase
• Fombone (2003) : review of 32 studies
 1966-1991 : 4,4/10.000
 1992-2001 : 12,7/ 10.000
• ADDM 1 : 150 (2002) ; 1: 110 (2006 )
• England 1:86 (2006) ; 1: 64 (2009)
• CDC 9 / 1000 (2006) ; 1 : 110 (2010)
• NHS (2013) : school age 2007-2012 : 1:50
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 Etiology

Exact etiology unknown yet  multifactorial

Risk Factors:
1. Disorders at prenatal, natal, postnatal.

2. Environment.

3. Metabolism disorders

4. Genetic
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 Risk Factors

1. Prenatal, natal and postnatal factors :

mother age (>35 years old), risk 3x > compared
to 20 years old,
Increasing age of 10 years : mother risk ↑ 38%
and father risk ↑ 22%
Hemorrhage and infection at pregnancy, low
birth weight infants, low APGAR score,
hyperbilirubinemia, febrile convulsion, etc

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Neurona vol 22 no1 Oktober 2004
• 2. Environment :

a. Heavy metal pollution : Hg, Pb

99% : heavy metal metabolism disorders due
to metallothionine defect
Responsible in immune responses,
neurodevelopment, heavy metal detoxification
Clasiccal symptoms of autism: GI disorders,
heavy metal sensitivity, abnormal behavior

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• 2. Environment :
b. Vaccination :
DPT/MMR → Thimerosal : ?
→ Neurotransmitter disorders: dopamine,
serotonine, glutamate, norephinephrine,
acetilcholine.
→ Poisoning ~ autism : socialization disorder,
stereotype behavior, depression, anxiety

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3. Metabolism disorders :

Food Allergic :
Flour → Glutein
Milk → Casein

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4.Genetic

• Family history of autism exists → Risk of 3-8%

• Monozygote twins → risk 70-90%
Dizygote twins → 0-3%
• Related to other syndromes : x fragile
• Lesion of 15q11-q13 → GABA
• Lesion of 17q11.2 → serotonine

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TRIAD of AUTISM :

1.Communication disorder

2.Social interaction disorder

3.Behavior disorder
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1. Communication disorders
• Verbal (speaking) and non verbal (signal)
communication

• Verbal disorders range from: mutism to verbal

fluency
~ confusing in communicating

• As if a child with hearing disorder

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 2. Social interaction disorders
• Feeling uncomfortable in his parents cuddling

• Avoiding eye contact

~ as if rejecting attention/affection

• Not showing pleasure when parents come/not

dissappointed when parents go

• Difficult to understand other’s

feeling/thinking/expression

• Prefer to be alone
• Agressive, self injury behavior, low intelligence
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3. Behavior disorder

• Realized by parents, at 2-3 years old

• Repetitive bizarre movements (stereotype) :
waving hand/arm, shaking body/things, etc
• Same game objects, for hours
• No imagination & creativity
• Obedience, sameness ~ ritual
• Hyperactive,aggressive,impulsive,destructive
• Sensitivity to odor, sounds, pain
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Disorders of Brain Anatomy

a. Amygdala  dense and small

neuron  control aggressivity,
emotional

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Struktur minikolum autis ( sisi kanan) lebih rapat
b. Hippocampus  dense and small
neuron  memory and learning disorder

c. Frontal lobe disorder in planning

action

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d. Temporal lobe  disorder of listening
and speaking
e. Reticular Activating System (RAS)
 centre of consciousness

f. Cerebellum  purkinye cell  

serotonine   disturbances of
neuron communication in brain

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Ggn Cerebelum pd autism

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• Bukti in Vivo:
– ↓ukuran dari satu/lebih region di vermis
serebellar → lobulus vermis VI-VII

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• Lobus Anterior
Menerima rangsang dari medulla spinalis dan
mengontrol otot anti-gravitasi tubuh (mengatur
postur tubuh)

• Lobus Posterior
Berhubungan dengan koordinasi gerakan otot
dengan cara menghambat gerakan otot yang
sifatnya tidak disadari (involunter)

• Lobus Flocullonodularis
Berfungsi mempertahankan keseimbangan

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• Laporan post-mortem yang menyebutkan :
hipoplasia lobular vermis, terutama yang
mempengaruhi posterior lobulus VI-VII

• Dengan demikian, hipoplasia vermis,

khususnya lobulus VI-VII, dapat
berhubungan dengan AD tetapi hubungan
ini tidak pasti dan ada heterogenitas
dalam AD.

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 Beberapa Penelitian :

Disfungsi cerebellar yang mendasari

Defisit Motor dan Kognitif dalam
Gangguan Autistik (MW Mosconi, JA
Sweeney) , 2002

• Jalur sensorimotor : lobulus anterior I-V

dan lobulus VIII. Sebaliknya, fungsi
kognitif terutama melibatkan lobulus
posterior VI-VII / Crus I-II
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• Gangguan motorik pada AD
Penelitian terbaru : gangguan kontrol
vestibular, dan kelainan motorik kasar dan
halus serupa dengan yang ditunjukkan
oleh pasien dengan penyakit cerebellar.

Freitag et al., 2010: menemukan bahwa

gangguan motorik kasar dan halus
berhubungan dengan keparahan gejala
autis .
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• Townsend et al, 2011: menemukan
perhatian yang lebih lambat terkait dengan
penurunan volume dari lobulus Vermis VI-
VII.

Beberapa fungsi memori terganggu

dalam AD, meskipun ada bukti bahwa
sejauh mana subjek terganggu sangat
terkait dengan kompleksitas tugas

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 Implikasi Kelainan Serebellar pada
Autisme
• Gangguan Fungsi
Diketahui bahwa fungsi serebelum sebagai
pengantisipasi dan prediksi atau fungsi persiapan
(preparation)
gangguan fungsi persiapan (preparatory) dengan
gejala : gangguan interaksi sosial dan gangguan
komunikasi

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• Gangguan Konektivitas
↓neuron Purkinje akan mengarah pd
gangguan penyimpangan aktivitas dari serebelum
ke regio otak lain (sepanjang lintasan serebellum-
thalamus-korteks serebral) yang menyebabkan
terjadinya defisit sosio emosional yg menonjol
pada autism

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 Therapies in Autism:
• 1. Pharmacotherapy

• 2. Exercise Therapy / Physiotherapy

• 3. Biomedical Therapy

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 1. Pharmacotherapy

• Medical therapy based on symptoms

– Speaking disorder : piracetam (becareful)
– Hyperactive ; methylphenidate
– Aggressive / tantrum : SSRI, risperidone
– Seizure : valproate acid

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Exercise Therapy :

• Speech therapy

• Behavior therapy

• Sensory integration

• Occupational therapy

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Biomedical Therapy
 G.I.Tract disorder : - enzyme, probiotics ,
antifungal ,anti bacteria.

Food Allergic : healthy food

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A cuh tak acuh
U sil,banyak gerak
T erlambat bicara
I majinasinya hilang
S ulit kontak mata
M onoton gerakannya
E mosi datar
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Terima Kasih

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