Professional Documents
Culture Documents
Algorithms in Pediatric Neurology 2011 Jaypee
Algorithms in Pediatric Neurology 2011 Jaypee
Pediatric Neurology
Mission
To write a non-boring book which can solve some problems of a busy pediatrician.
Besides the noble art of getting things done, there is the noble art of leaving things undone.
The wisdom of life consists in the elimination of non-essentials.
— Lin Yutang
Algorithms in
Pediatric Neurology
(A Beginner’s Guide)
Corporate Office
4838/24 Ansari Road, Daryaganj, New Delhi - 110 002, India
Phone: +91-11-43574357, Fax: +91-11-43574314
Offices in India
• Ahmedabad, e-mail: ahmedabad@jaypeebrothers.com
• Bengaluru, e-mail: bangalore@jaypeebrothers.com
• Chennai, e-mail: chennai@jaypeebrothers.com
• Delhi, e-mail: jaypee@jaypeebrothers.com
• Hyderabad, e-mail: hyderabad@jaypeebrothers.com
• Kochi, e-mail: kochi@jaypeebrothers.com
• Kolkata, e-mail: kolkata@jaypeebrothers.com
• Lucknow, e-mail: lucknow@jaypeebrothers.com
• Mumbai, e-mail: mumbai@jaypeebrothers.com
• Nagpur, e-mail: nagpur@jaypeebrothers.com
Overseas Offices
• North America Office, USA, Ph: 001-636-6279734
e-mail: jaypee@jaypeebrothers.com, anjulav@jaypeebrothers.com
• Central America Office, Panama City, Panama
Ph: 001-507-317-0160
e-mail: cservice@jphmedical.com, Website: www.jphmedical.com
• Europe Office, UK, Ph: +44 (0) 2031708910
e-mail: info@jpmedpub.com
All rights reserved. No part of this publication should be reproduced, stored in a retrieval system, or transmitted
in any form or by any means: electronic, mechanical, photocopying, recording, or otherwise, without the prior
written permission of the author and the publisher.
This book has been published in good faith that the material provided by author is original. Every effort is
made to ensure accuracy of material, but the publisher, printer and author will not be held responsible for any
inadvertent error(s). In case of any dispute, all legal matters are to be settled under Delhi jurisdiction only.
This book aims to simplify and demystify some of the common problems in pediatric
neurology especially encountered by the general pediatricians and pediatric students (both
undergraduates and postgraduates). It tries to describe a practical approach towards the
diagnosis and treatment of various neurological conditions which would prove extremely
useful in day to day clinical practice.
Pediatric neurology has come a long way. There was a time when a pediatrician’s best
advice was to tell the parents to simply wait and let the child outgrow his problems. Today
magnetic resonance imaging, genetics and basic science related to the understanding of
complex illnesses have changed the way we handle these problems.
However, the clinical approach to most problems can be further simplified. This book,
titled Algorithms in Pediatric Neurology intends to enable the ordinary pediatrician to
recognize many disorders in a simplified manner and give practical suggestions in their
management. These algorithms are based on the concept of listening, watching and thinking
before initiating treatment.
I plead guilty to the sins of oversimplification and a happy disregard for details. But it
is in the larger good of empowering the general pediatrician and student of pediatrics to try
to look at and understand pediatric neurology problems.
Unstinting support from my family kept me going through this project and the naïve
questions from my students will always inspire me to look for simple solutions to difficult
problems.
Index......................................................................................................................... 73
1
A Child with a Large Head
Children come in all shapes and sizes. The same is true of their heads. Sometimes a child’s
head seems disproportionately big. You need some kind of algorithm to first confirm that it
is abnormally large. Second, decide the possible cause. And finally you need to see whether
the child needs some intervention or just masterly inactivity.
Step I
Is the head abnormally large?
Macrocephaly is defined as a head circumference > 2 SD for that age.
Measure the head circumference properly over midforehead and most prominent part of
occiput posteriorly.
If you have serial recordings of head circumference, a rapid increase deviating from the
patient’s previous growth trajectory is more ominous.
Also measure the child’s height and weight. If head circumference, height and weight all
are > 95th centile the child is likely to be normal or with one of the overgrowth syndromes
like Sotos syndrome. If only head circumference is > 95th centile, there is likely to be an
abnormality.
In newborns, a rule of thumb, till 36 weeks is as follows: if the head circumference in
cm is > than the weeks of gestation, the head is large, e.g. A 32-week-old newborn with a
head circumference > 32 cm has macrocephaly.
Gestation in weeks Upper limit of head circumference in cm
28 28
30 30
32 32
34 34
36 36
38 37
40 38
42 39
44 40
2 Algorithms in Pediatric Neurology
In preterms the rate of growth is generally 0.5 cm in first 2 weeks, 0.75 cm in the 3rd
week, 1 cm from 4th week onwards till 40th week of gestation.
After the new born period the rate of growth is as follows:
Age Growth of head circumference in cm/month
0-3 month 2
3-6 months 1
6-12 month 0.5
1-3 years 0.25
4-6 years 1 cm/year
For older children upper limits of head circumference at various ages need to be plotted
on centile charts. A rough guide is as follows:
Age 95th centile head circumference (cm)
2 months 43
4 months 45
6 months 46.5
8 months 47.5
10 months 48.5
1 year 49
1.5 years 50.4
2 years 51.3
2.5 years 52
Step II
What is the etiology?
A Child with a Large Head 3
Step IIa
Totally normal child
Disease Clinical clues Tests
Familial megaloencephaly Family history of large heads. Head MRI normal
circumference normal at birth,
progressively increases to reach 98th
centile. Normal development and
physical examination
Benign enlargement of subarachnoid Familial, autosomal dominant, head CT or MRI brain:
space/external hydrocephalus circumference 90th centile at birth enlarged subarachnoid
and increases to follow 98th centile, space in frontal region
wide open anterior fontanelle, normal > 5.7 mm, in sylvian
development and examination. Due to fissure >7.6 mm
development delay in reabsorbtion of
CSF in arachnoid villi. Predisposed
to subdural bleeds with minor trauma.
Step IIb
Neurologically normal child with abnormal systemic findings
Disease Clinical clues Tests
Rickets Frontal bossing, wide wrists, bow Alkaline phosphatase ↑, X-ray: cupping
legs and fraying of metaphyses
Achondroplasia Asymmetric short stature with Primary X-ray criteria: (i) Decrease in
short limbs, normal intelligence interpedicular distance in the lumbar spine;
but may have delayed motor (ii) square short ilia; (iii) short, broad neck
development, may later develop of femur; (iv) shortening of long tubular
cervical spine compression bones, with metaphyseal flaring;
(v) Brachydactyly
Genetic tests: FGFR 3 mutation
Step IIc
If there are abnormal neurological symptoms or signs:
Is there evidence of raised intracranial pressure: Clinical signs include a tense anterior
fontanelle, open posterior fontanelle after 2 months age, open sutures, dilated veins on the
scalp, sunsetting, headaches, early morning vomits, brisk jerks in lower limbs, upgoing
planters, bradycardia, hypertension.
Causes of large head with evidence of raised intracranial tension are—hydrocephalus
both obstructive and communicating and chronic subdural effusion.
Disease Clinical clues Tests
Aqueductal stenosis Congenital, post infectious or CT or MRI: Mickey mouse ventricles:
inflammatory. Sporadic or both lateral and third ventricles are
X recessive. Progressive increase ballooned out and fourth is undilated.
of head size from early infancy,
associated spina bifida, dilated
veins on scalp.
Dandy-Walker cyst Prominent occiput, associated MRI: (i) cystic dilatation of 4th
migration defects like cortical ventricle (ii) cerebellar hypoplasia
dysplasia, ataxia, nystagmus, (iii) hydrocephalus due compression
cranial nerve palsies, lower limb of posterior fossa cyst or aqueductal
hyperreflexia, seizures. stenosis.
Communicating Subacute h/o fever, progressive CT/ MRI: Dilatation of all four
hydrocephalus in TBM drowsiness, seizures, neck rigidity, ventricles, basal exudates, infarcts
cranial nerve palsies, focal deficits especially basal ganglia and
like hemiparesis. brainstem, calcification, inflammatory
granulomas.
Step IId
Is there history of neuroregression?
Disease Clinical clues Tests
Leukodystrophies Onset in infancy, loss of MRI: bilateral symmetrical white
(metachromatic motor and mental milestones, matter hyperintensity on T2
leukodystrophy, Canavans abnormalities of tone, autosomal suggesstive of cerebral edema.
syndrome, Alexanders) recessive inheritance (Alexanders – abnormalities with
frontal prominence, periventricular
rim bright on T1, Cananvans –
NAA peak on MR spectroscopy,
MLD: deficiency of arylsulphatase)
Glutaric aciduria I Normal at birth, deteriorate after MRI—bat wing appearance due
acute illness, choreoathetosis and to wide sylvian fissures, urine
extrapyramidal signs, progressive and blood organic acids are
neuroregression confirmatory.
Step IIe
Are there soft neurological signs/ learning disabilities with a large head
Disease Clinical clues Tests
Sotos syndrome Large baby, tall, big jaw, pointed Mutations in NSD 1
chin, funny facies, mild intellectual
retardation, learning disabilities
Fragile X Long face, protruding ears, DNA PCR or Southern blot for CGG
high arched palate, large testes, repeats
hyperflexible joints, behavioral and
cognitive deficits
6 Algorithms in Pediatric Neurology
Step III
What is the management?
Specific management according to cause are as follows:
Disease Management
Familial megaloencephaly Reassurance
Benign enlargement of subarachnoid space Reassurance
Aqueductal stenosis Ventriculoperitoneal shunt, third
ventriculostomy
Dandy-Walker cyst Cystoperitoneal or ventriculoperitoneal or
dual shunt
Communicating hydrocephalus in TBM Ventriculoperitoneal shunt
Posthemorrhagic hydrocephalus in preterms VP shunt when weight > 1500 gm and CSF
RBCs < 1000/cc, CSF protein <500 mg/cc
Chronic subdural effusion Surgical drainage
Glutaric aciduria I Lysine restricted diet, supplement with
riboflavin and carnitine. Valproate and
baclofen may have a role.
Bibliography
1. Garg BP, Walsh L. Clinical approach to the child with a large head. Indian J Pediatr 2001;68 (9):867-71.
2
A Child with a Headache
Though children are often implicated as a cause of headache, it is less recognized that they
are also legitimate sufferers of headache.
They suffer most of the common types of adult headache including migraine, tension type
headache and other more sinister headaches. But, cluster headaches are distinctly uncommon
in childhood. It needs a keenly observant and empathetic adult to recognize headaches in
very young children. They may just present as unusual behaviors including head banging,
inexplicable crying, unexplained decline in normal activity, or other paroxysmal disturbances
like vertigo or abdominal pain.
Pain in meningitis is due to dilatation and inflammation of meningeal vessels and me-
ninges.
In many cases of tension type headache, psychological factors predominate. Excessive
contraction of neck, forehead and jaw muscles are often found. Pain threshold seems to be
lower than average and there may be a primary failure of the brains endogenous pain control
system.
Clinical approach
Tension Headache
This headache is dull and not as severe as migraine. It is continuous. It continues throughout
the day and can persist for many days. But, it may disappear on Sundays and holidays. It
A Child with a Headache 9
does not interfere with daily activities. It is more common near adolescence. Underlying
depression and anxiety is common.
Raised ICT
Headaches due to intra cranial space occupying lesions, e.g. tumor, hydrocephalus or chronic
meningitis increase progressively in severity and frequency. They may wake the child from
sleep. Associated symptoms include vomits, blurred vision, seizures, loss of consciousness
and leg weakness.
Miscellaneous Conditions
The common clinical scenario when a pediatrician encounters a child with a headache is
often with a febrile illness. Significant headache with the fever must alert the pediatrician
to rule out meningitis, though it is more commonly found with typhoid, sinusitis, and some
viral fevers.
Sinusitis
The headache is localized to forehead, maxilla or periorbital region. You may get local ten-
derness over the region. In frontal and ethmoidal sinusitis, the pain worsens on awakening
and gradually subsides when patient remains upright. The opposite is true with maxillary
and sphenoidal sinusitis.
Ocular Disorders
Hypermetropia and astigmatism (rarely myopia) may induce a dull aching headache after
long use of the eyes in close work. Location is usually periorbital. It is due to over contrac-
tion of extraocular muscles along with frontal and temporal muscles.
Investigations
1. The most useful investigation is a careful history and examination.
2. An EEG is mostly useless in the work up for headaches.
10 Algorithms in Pediatric Neurology
Management
Migraine
a. Reassurance that it is not a brain tumor reduces headaches significantly.
b. Avoid precipitating factors like excessive light, sun, loud noises, missing meals, un-
necessary stress, foods (e.g. chocolates, nuts, chinese foods, citrus foods, cheese, etc.).
c. Reducing exposure to short wave-length flicker from fluorescent lights by wearing rose
tinted glasses has been shown to reduce headaches in children from 6.2 to 1.6 per month
over a period of 4 months.
d. Check posture of the child. If height of chair and desk are mismatched child assumes
abnormal postures to study which need correction.
e. Regular mealtimes and adequate sleep are paramount.
f. For an acute attack
i. Use an analgesic like acetaminophen (15 mg/kg), ibuprofen (7.5 mg/kg)
ii. Add an antiemetic if required.
iii. Let the child sleep in a quiet, dark room.
iv. For those resistant to common analgesics triptans are an alternative. Sumatriptan nasal
spray (5 mg < 25 kg, 10 mg for 25-50 kg, 20 mg > 50 kg) is effective. Dose may be
repeated after 2 hours, a maximum of 2 times in 24 hours. Subcutaneous sumatriptan
0.06 mg/kg is also effective. Oral sumatriptan seems to be less efficacious. The main
side effects of triptans are coronary vasospasm and hypertension.
v. Rizatriptan (5 mg for 12-17 years) and Zolmitriptan (2.5-5 mg for 12-17 years) have
also been tried.
vi. Ergot preparations are less preferred in childhood though cheaper than triptans.
vii. IV prochlorperazine (Stemetil) 0.15 mg/kg (max 10 mg) is useful in status migranosus.
viii. Prophylaxis for headache is required if migraine attacks are too frequent (>2-4/month)
or interfering with school attendance. Flunarizine 5 mg at night is most well documented
to be effective in children. Increase to 10 mg as required. Wait for at least 4 weeks for
efficacy. Propranalol 10-20 mg bid to tid is the next option if child is not asthmatic.
Use for 4-12 months. If child is underweight, cyproheptadine (0.2-0.4 mg/kg) has the
double benefit of weight gain and migraine prophylaxis.
A Child with a Headache 11
ix. Other drugs which have been used in prophylaxis include valproate (5-20 mg/
kg/d), topiramate (3-9 mg/kg/d), gabapentin (900-1200 mg/d), amitriptyline
(0.1-2 mg/kg/hrs).
Bibliography
1. Lance JW, Goadsby PJ. Mechanism and management of headache. Elsevier: Philadelphia, 2005.
2. Practice parameter. Evaluation of children and adolescents with recurrent headaches. Neurology
2002;59:490-98.
3. Practice parameter. Pharmacological treatment of migraine headache in children and adolescents.
Neurology 2004;63:2215-24.
3
A Child with School Failure
Introduction
A child may not learn upto expectations due to myriad reasons. But when a parent comes to
a pediatrician with the specific complaint of learning problems in a child who is physically
healthy, there is likely to be an important underlying cause. This chapter is to understand
how to approach a child with a learning disability (LD).
Why it happens
The basis for learning disabilities is both genetic and environmental. Nine loci DYX 1 to 9
have been linked to dyslexia. Inheritance is polygenic.
Studies in adults who developed alexia (inability to read) after a stroke first gave a clue
that reading is localizable to three major areas in the brain. The left posterior parietotemporal
region is required for word analysis, the left occipitotemporal area is the “word form area”
and the left inferior frontal region is for articulation and skilled automatic reading. In a child
with a learning disability it is just some of these areas which are not functioning perfectly
while the rest of the brain is just fine.
To be able to read a child must develop the insight that a spoken word can be broken up
into sounds (phonemes) and they represent parts of a written word (graphemes). The ability
to link the phoneme to a grapheme is missing in children with LD.
A Child with School Failure 13
Algorithm
Clinical features of LD
a. Unexpected difficulty in learning most commonly in reading (dyslexia) in a child who
otherwise has enough intelligence and motivation to learn is called learning disability.
b. Difficulty in reading is called dyslexia, in writing is dysgraphia and in mathematics is
called dyscalculia.
c. There is often a family history of learning problems in 23-65%.
d. In preschool there may be a history of trouble learning nursery rhymes. They are confused
between right and left.
e. Often the child fails to learn the letters of the alphabet by kindergarten.
f. He cannot find rhyming words.
g. By class one he has not learnt to read.
h. Parents and teachers are puzzled why this otherwise bright child has extreme difficulty
in learning to read. Writing is very untidy, with spelling errors. Letter (b for d) and word
inversion (saw for was) is common.
14 Algorithms in Pediatric Neurology
i. In older children when asked to read a passage: accuracy, rate, fluency and comprehen-
sion are under par.
j. The child progressively falls behind and self esteem is very low.
Differential diagnosis
a. Slow learner: He is overall slow with an IQ between 70 to 90
b. ADHD: Look for hyperactivity, inattention and impulsivity
c. Pervasive developmental disorders: Look for evidence of poor social interaction, limited
interests and abnormal motor mannerisms
d. Hearing deficit
e. Visual deficit
f. Psychological problems: Anxiety and depression may be the underlying reason for poor
school performance
Investigations
Hearing Assessment
Children with severe to profound hearing loss obviously have marked limitations in speech
and language. But even those with mild to moderate sensorineural hearing loss with thresh-
olds from 20 to 60 db have lower scores on language and academic achievement. However
conductive losses due to middle ear effusions have not been documented to have poor
outcomes related to language, speech or academics.
Vision Assessment
Treatable vision defects like refractory errors, strabismus, eye muscle imbalance and mo-
tor fusion defects must be looked for. However there is no evidence that eye defects subtle
or severe can cause any of the features of learning disabilities like letter or word reversal.
Psychological Assessment
Anxiety and depression may be the primary cause for poor academic achievement. Some-
times they are secondary to the learning disability.
Achievement Scores
The Woodcock-Johnson Psychoeducational battery and the Peabody Individual Achievement
Test are often used to assess academic achievement. The GLAD (Grade Level Assessment
Device) has been standardized for Indian children. Achievement scores which are 1-2 grades
below their IQ levels are used as markers of learning disabilities.
Response to Intervention
In the US currently “Response to Intervention” or RTI is used while making a diagnosis of
learning disabilities. Any child who is not performing up to expectations undergoes educa-
tional intervention. Failure to respond to routine intervention is a marker of LD.
Management
The management of LD is mainly educational. In the early years the focus is on remedia-
tion. As the child grows older and demands of secondary school become excessive, bypass
strategies need to be introduced. In some states in India like Karnataka some children with
LD do not need to learn a 2nd or 3rd language.
Introduction
How human beings learn to speak so fluently, coherently, understand such complexities like
grammar, sarcasm, humor, and irony and make socially appropriate and relevant replies is a
minor miracle which is happening around us all the time. When this miracle fails it happens
at any of the innumerable steps of language acquirement. It needs patience and thought to
sort it out.
Clinical approach
Step I
Is language delayed, abnormal or has it regressed?
Step II
If language is delayed:
a. Is hearing abnormal (hearing impaired)?
b. Is nonverbal IQ abnormal (part of mental retardation)?
c. Are social milestones inappropriate—absence of joint attention, symbolic play and
reciprocation of affection (autism, pervasive developmental disorder)?
d. Is there motor hypotonia and some abnormalities in pragmatics (specific language im-
pairement)?
e. Is everything else normal (delayed maturation or late talker)?
Step III
If language abnormal (e.g. abnormal prosody or pragmatics)
a. Are social milestones abnormal (Aspergers)?
b. Is there underlying anxiety (e.g. in selective mutism patient does not speak in certain
social settings)?
c. Is there significant motor deficits, drooling, feeding difficulty (cerebral palsy, myopathy)?
d. Is there difficulty pronouncing syllables properly (phonological disorders)?
e. Are there oromotor difficulties, groping for words, grunting, inconsistent pronunciation
of words (verbal apraxia)?
f. Is there problems in fluency (stuttering)?
Step IV
Has language regressed (has he forgotten words and speech milestones he had learnt earlier)?
a. Are social milestones inappropriate (autism)?
b. Has he an acquired brain disorder (post-meningitis, encephalitis, etc.)?
c. Is the EEG abnormal (Landau-Kleffner syndrome [LKS] or epileptic aphasia, may have
persistent bitemporal epileptic discharges)?
d. Is there severe deterioration of mental and social functioning (childhood disintegrative
disorder)?
e. Is there regression of motor milestones, vision, cognition, etc. (neurodegenerative dis-
order)?
18 Algorithms in Pediatric Neurology
Management
i. In hearing impaired children, amplification with a hearing aid, speech therapy and
cochlear implants are the solution.
ii. In children with cognitive impairment a tailored program of special education is re-
quired.
iii. Autistic children need a specialized program of education, behaviour therapy and oc-
cupational therapy.
iv. In selective mutism and psychological dysphonia, psychological counseling and speech
therapy has remarkable results.
v. In stuttering we need to differentiate from developmental disfluency which children
overcome easily with time. However if there are > than 5 word breaks in 100 words,
it lasts for more than 3 months, is associated with feeling of stress and in an age
> 4 years they are best referred to a speech therapist.
Speech therapy for stuttering includes reducing parental criticism, improving self
esteem, timed syllabic speech (speaking syllable by syllable stressed evenly), shadow
method (repeating words spoken by a therapist), using universal fluency initiating
gestures like Slow, Deep, Loud, Smooth, instruments like delayed auditory feedback
and the Edinburgh masker. Bedtime reading to model slow and fluent speech is helpful
and drugs like haloperidol, risperidone and olanzapine are rarely required.
vi. In phonological disorders speech therapy with training of tongue and lip positions are
useful and 75% attain clear speech by 6 years in mild to moderate disorder.
vii. Landau-Kleffners syndrome is often treated with antiepileptics and steroids. Epilepsy
surgery such as multiple subpial transactions may have a role in refractory cases.
Bibliography
1. Prasse JE, Kikano GE. Stuttering: An overview. Am Fam Physician 2008;77(9):1271-6.
5
The Child with a Stroke
Definition
A child is said to have a stroke when a child has an acute onset neurological deficit like a
hemiparesis due to cerebral infarction of vascular origin as seen on either a CT or MRI as
ischemia or infarction or bleed.
Differential Diagnosis
An acute onset neurological deficit may also occur after prolonged focal seizures, after
hypoglycemia, prolonged post ictal state (Todd’s paresis), acute disseminated encephalo-
myelitis, meningitis, encephalitis, brain abcess and intracranial space occupying lesion.
20 Algorithms in Pediatric Neurology
Perfusion weighted imaging has been used to document the penumbra or tissue at risk.
Mass effect can start as early as 2 hours after onset, peaks by 24 hours and may occur
in absence of parenchymal changes.
With paramagnetic contrast, there is no parenchymal enhancement. There may be slow
flow in arteries with contrast in hyperacute infarcts and parenchymal and meningeal en-
hancement around 48 hours.
Acute Subtle low intensity Hyperintense, best >8 hrs DWI: ↑intensity even in first
few hours, ADC↑intensity in
cytotoxic edema, ↓intensity
in vasogenic edema
Subacute infarct Low signal High signal Vascular distribution, re-
(1 week or vascularization can cause
older): parenchymal enhancement
with contrast
Old infarct Low signal High Mass effect disappears after
(several weeks to 1 month. Loss of tissue with
years): large infarcts. Parenchymal
enhancement fades after
several months.
22 Algorithms in Pediatric Neurology
Thrombophilia Panel
Genetic
1. Factor V Leiden mutation
2. Prothrombin G20210 A polymorphism
3. Elevated plasma lipoprotein (a) concentration.
Genetic or acquired
1. Antithrombin deficiency
2. Protein C or S deficiency
3. Elevated factor VIII activity
4. Hyperhomocystenemia
5. Antiphospholipid antibodies (APA)
6. DIC
7. Activated protein C resistance.
Treatment
1. Stabilization of airway, breathing and circulation. Avoid hypotension.
2. Maintain euglycemia. Both hyper and hypoglycemia are to be avoided. Keep sugar
70-200 mg/dl.
3. Treat seizures.
4. Manage raised intracranial pressure.
5. Anticoagulation is indicated in venous sinus thrombosis, dissection and cardioembolic
stroke.
6. Anticoagulation may be done with unfractionated heparin (UFH) or low molecular
weight heparin (LMWH). LMWH is easier to use because it is given subcutaneously,
does not need so much monitoring and has less thrombocytopenia compared to heparin.
Heparinize for 5-10 days.
Heparin is used with loading dose 50-75 U/kg IV, maintenance of 50 U/kg/hr IV in
neonates, 15-25 U/kg/hr in children.
Keep APTT between 60-85.
Continue with oral warfarin after an overlap period of 2-3 days. Dose 0.1 mg/kg/day
OD. Tablet size 1, 2, 5 mg.
Maintain an INR between 2-3. Check PT after 5 days of starting then weekly till stable.
Discontinue warfarin 5 days before invasive procedures.
Continue anticoagulation for:
3-6 months, if there was underlying reversible risk factor.
6-12 months, if thrombosis was idiopathic.
12 months to lifelong, if there is a chronic risk factor.
In recurrent thrombosis anticoagulation is at least 6 months longer than indicated for
first thrombosis.
7. Recommendations for anticoagulants in acute ischemic stroke are variable. The Royal
College of Physicians recommend aspirin (3-5 mg/kg/d) and not anticoagulants.
8. The American College of Chest Physicians recommends heparin for all non sickle cell
anemia stroke for 5-7 days till cardioembolic stroke and dissection is ruled out.
The Child with a Stroke 25
9. Oral anticoagulation is continued for 1 year in cardioembolic stroke and 3-6 months
in dissection.
10. All anticoagulation is to be followed by long term aspirin.
11. Stroke in sickle cell anemia is treated with exchange transfusion to reduce HbS to
< 30% which is to be maintained with a long-term transfusion therapy. If exchange
transfusion is delayed more by than 4 hours give top up transfusion to correct severe
anemia. Hydroxyurea may be used when long-term transfusions are not possible.
12. In neonatal stroke only supportive therapy is used. Antiplatelets and anticoagulation
are rarely used. If a potent thrombophilic state is identified, antithrombotic therapy can
be considered in a case by case basis.
13. In hyperhomocystenemia intervention with diet, folate, vitamin B6 and B12 is recom-
mended.
14. In Moya moya syndrome surgical revacularization procedures are used, especially if
patient has cognitive decline or recurrent or progressive symptoms. Anticoagulants are
generally not recommended due to risk of hemorrhage. Antiplatelet agents have been
used in patients with mild disease, in whom surgery is risky and patients with ischemic
symptoms due to microemboli.
15. Autoimmune vasculitis may require corticosteroids and cytotoxic drugs such as pulse
cyclophosphamide.
16. Recombinant tissue plasminogen activator rtPA is not yet standard recommendation in
pediatric stroke pending more clinical data.
Bibliography
1. Management of stroke in infants and children: A scientific statement from a Special Writing Group of the
American Heart Association Stroke Council and the Council on Cardiovascular Disease in the Young.
2. Roach ES, Golomb MR, Adams R, Biller J, Daniels S, Deveber G, Ferriero D, Jones BV, Kirkham FJ,
Scott RM, Smith ER. American Heart Association Stroke Council; Council on Cardiovascular Disease in
the Young Stroke 2008; 39(9):2644-91.
6
Approach to a Child with an
Inborn Error of Metabolism
In our body substances are constantly being converted into other compounds by a series of
enzymatic reactions. The enzyme acts on a substrate to create a product. Blocks in these
reactions result in imbalances of substrates and products which may have clinically evident
effects.
C
A B
ASA—Argininosuccinic acid
CPS—Carbamoyl phosphate synthetase
OTC—Ornithine transcarbamylase synthetase
Diets deficient in branched chain amino acids are available as commercial formulas. Long
term prognosis is guarded, though some children have done well after liver transplant.
Organic Acidemias
These occur due to deficiency of enzymes in the catabolism of various amino acids such as
isoleucine, valine, methionine, threonine, leucine and lysine resulting in the accumulation
of various organic acids. They include:
• Methylmalonic acidemia (MMA)
• Propionic acidemia (PA)
• Isovaleric acidemia
• Glutaric acidemia type I
• 3-Hydroxy-3-methylglutaryl CoA lyase deficiency
• 3-Methylcrotonyl-CoA carboxylase deficiency
Neonates become symptomatic a few days after starting feeds. They develop lethargy,
vomits, seizures, rash, abnormal smell and a sepsis like syndrome.
Investigations may show severe ketoacidosis, lactic acidosis, hyperammonemia,
hypoglycemia, thrombocytopenia and neutropenia.
The acylcarnitine profile on tandem mass spectroscopy will show the following eleva-
tions:
• Glutaric acidemia type I—C5DC
• Propionic and methylmalonic acidemia—C3
• Isovaleric acidemia—C5
• 3-Hydroxy-3-methylglutaryl CoA lyase deficiency—C5OH
• 3-Methylcrotonyl CoA carboxylase deficiency—C5OH
Treatment includes low protein diet, restriction of the implicated aminoacids, carnitine
supplements, vitamin supplements and avoidance of fasting. The vitamins supplements
include vitamin B12, 1 mg/d in MMA and biotin in PA.
Lactic Acidosis
1. Check lactic acid is elevated.
2. Check tandem mass spectroscopy.
3. If acylcarnitine profile on TMS is abnormal consider organic acidemia or fatty acid
oxidation defect.
4. If TMS is normal check pyruvate, blood sugar and cardiac and multisystem involvement.
5. Use the following algorithm to go further.
30 Algorithms in Pediatric Neurology
Step II
Was the onset of the disease with predominantly symptoms and signs related to grey matter
or white matter involvement?
Signs and symptoms Grey matter disease White matter disease
Seizures Early, prominent Late, rare
Cognitive decline Early and progressive Initially normal
Head size Often small Often large
Spasticity Late Early, severe
Deep tendon reflexes Exaggerated Depressed/ variable
Fundus Retinal degeneration Optic atrophy
Cerebellar signs Late Common
EEG Epiletiform discharges Diffuse slowing
NCV Normal Often slowing of
velocities
Examples Leighs, Alpers, Menkes kinky hair Leukodystrophies
disease
Approach to a Child with an Inborn Error of Metabolism 31
Step III
Besides white and grey matter degenerative disorders others may present with significant
basal ganglia or cerebellar involvement. Examples of all four groups are as below:
Step IV
A rather simplistic approach to neuroregression is given below:
32 Algorithms in Pediatric Neurology
Bibliography
1. Burton BK. Inborn Errors of Metabolism in Infancy: A Guide to Diagnosis. Pediatrics 1998;102.
7
The Child with Cerebral Palsy
A normal child constantly attains milestones in various domains- motor, cognitive, language
and social. When he fails to do so, we must discriminate whether he has a normal variation,
a delay or a loss of previously attained milestones. We also need to know whether it is in one
domain or many. The domain in which the delay occurs also helps to classify the problem.
A child with cerebral palsy will have predominantly a delay in motor milestones.
Algorithm
Therapeutic Modalities
1. Physiotherapy
2. Plaster casts, orthoses
3. Adaptive devices
4. Antispasticity drugs
5. Botulinum toxin
6. Surgery
7. Treatment of associated problems.
Principles of Physiotherapy
1. Correct positioning
2. Adequate stimulation
3. Encourage movements especially in activities related to daily living
4. Prevent contractures.
Adaptive Devices
Are used to improve position and make child independent in activities of daily living, e.g.
crutches, wheelchairs, hand splints, adapted tooth brush and cup, etc.
Antispasticity Drugs
Drugs Mechanism of action Dose Side effects
Baclofen Inhibits transmission Start with 2.5-5 mg/day in dd. Drowsiness
at spinal level by Maximum 40 mg (< 7 years), 60 mg
hyperpolarization of the (> 7 years)
afferent nerve terminal
Botulinum Toxin
How does it work?
Intramuscular injection of a small amount of botulinum toxin type A into a muscle inhibits
the release of acetylcholine at the neuromuscular junction causing a chemical denervation.
The aim is to reduce excessive muscle activity without excessive weakness.
It is used to
1. Improve function
2. Cosmesis
3. For ease of nursing care.
Dosage
There is no fixed dose recommended. It depends on the size of the muscle. The aim is to
get clinical response without excessive weakness.
Dose is around 1-2 U/kg (small muscles), 4-6 U/kg (large muscles); maximum 12 U/kg
(not to exceed 400 U/kg). May need to be repeated every 4-6 months when effect wears off.
Approach
A neonate comes with history of repetitive motor movements suggestive of seizure.
Step I
Stabilize ABC.
Step II
Take samples for blood sugar, serum calcium and magnesium.
Step III
• Give 2-4 ml/kg of IV Dextrose 10%
• 2 ml/kg of IV calcium gluconate
• 0.2 ml/kg of IM MgSO4
Step IV
• Take detailed history and examination of possible etiologies
• If seizure continues start IV Phenobarbitone 20 mg/kg slowly over 20-30 minutes
watching for respiratory depression.
Step V
If no response repeat with 5 mg/kg upto a total of 40 mg/kg of phenobarbitone. Continue
maintenance of 5-8 mg/kg/d.
Step VI
If seizure persists or patient drowsy miss previous step and load with IV phenytoin 20 mg/kg
slowly over 20-30 minutes. If no response reload with 5 mg/kg upto 40 mg/kg/d. Continue
maintenance of 5-8 mg/kg/d.
40 Algorithms in Pediatric Neurology
Step VII
If seizures persist give midazolam 0.02-0.1 mg/kg, then infusion of 0.01-0.06 mg/kg/min.
Step VIII
• Seizures persist, use IV pyridoxine 50-100 mg
• If unavailable use IM pyridoxine 50-100 mg (e.g. Inj Optineuron)
• If unavailable use oral pyridoxine 50-100 mg (e.g. Tab Benadon).
Step IX
Unresponsive; etiology unclear: Use oral folinic acid 2.5 mg BD (e.g. Leukovorin)
(max 8 mg/kg/day). Investigate for other metabolic disorders.
Step X
Unresponsive seizures (etiology clear, e.g. HIE, structural malformation, meningitis) use
IV Valproate, IV Levetiracetam.
Investigations
Stage I
• Blood sugar, S. calcium, S. magnesium
• Septic profile (CBC, blood culture), CSF.
Stage II
• Neuroimaging:
• Unstable patient, preterm, suspicion of IVH: USG cranium
• Stable patient, term, suspicion of bleed (SAH, Subdural): CT head
• Dysmorphic patient, stable, CT normal, persistent seizures: MRI brain.
Stage III
• Electroencephalogram (EEG).
• See background.
• Look for seizure activity.
• See EEG response to injectable pyridoxine.
• If IUGR, hepatosplenomegaly, cataract, etc.—IgM TORCH.
Stage IV
• Persistent seizures
• Abnormal smell, rash, unexplained lethargy, consanguinity, family h/o neonatal deaths:
The Neonate with Seizures 41
• Work-up for inborn errors of metabolism: S. ammonia, ABG, S. lactate, urine ketones
• Urine and serum amino acids, organic acids (a tandem mass spectroscopy screens for
many together).
Stage V
• Persistent seizures
• EEG to look for any abnormal pattern like burst suppression
• CSF aminoacids (nonketotic hyperglycinemia), CSF lactate (respiratory chain abnormali-
ties).
• Low CSF sugar with normal blood sugar may give a clue to glucose transporter defect
and responds to ketogenic diet.
Stage VI
Onset day 1 to 7, persistent seizures, normal neurology and development, positive family
history, spontaneous resolution after days to weeks, diagnosis of exclusion: Consider the
benign neonatal seizure syndromes.
9
The Child with Seizures
Step I
Is it a seizure?
a. Ask for a complete description of the seizure event. One of the best ways is to ask the
parent or person who has observed the event to enact it. It is surprisingly very accurate.
b. Events which point to it being a seizure include absence of a precipitating event, tonic
deviation of the eyes, urinary incontinence and tongue bite. A history that the child went
off to sleep after the event is usually seen in a seizure.
c. Home video recordings may help to confirm diagnosis in case of doubt.
Step II
Rule out common conditions which are often confused for a seizure but are not.
a. Breath holding spells: Cyanotic breath holding spell occurs between 6 months to 5
years, precipitated by a tantrum followed by crying, and culminates in breath holding
with cynosis and minor clonic movements. A pallid breath holding spell follows minor
injury to the head, followed by pallor and loss of tone.
b. Syncopal attacks: Benign neurocardiogenic syncope is usually precipitated after pro-
longed standing, fasting and heat. Prodromal symptoms like sweating, nausea may occur.
It is brief—10 seconds. The skin is cold, pale and clammy. There is quick recovery after
lying down. Basic work up includes a hemoglobin, ECG to rule out arrythmias and a tilt
table test.
c. Migraine: Differentiating features include:
Clinical features Migraine Epilepsy
Sensorium Clear Usually drowsy
Duration Hours Minutes
Aura Usually visual Visual, olfactory, sensory, etc.
Family history Of migraine common Sometimes positive for epilepsy
Onset Gradual Sudden
EEG Nonspecific abnormalities Spikes and sharp waves
The Child with Seizures 43
d. Night terrors: Are episodes of intense fear and panic which occur in children between
2-6 years. It occurs in the first 2-3 hours of sleep, child is screaming and crying but dif-
ficult to arouse. There may be a family history. Fatigue, sleep deprivation, violence on
TV may be precipitating events. It may last a few minutes to an hour but the child has no
memory of the event later. Children outgrow it and oral diazepam may help occasionally.
e. Prolonged QT syndrome: Must be suspected in exercise induced syncopal episode
especially with a family history. The corrected QT interval is > 0.44 secs.
Step III
What is the type of seizure?
You need to know this because it helps you decide which antiepileptic to use and gives a
clue as to possible etiologies.
Is it absence seizure?
Typically in 6-12 years olds, there is a sudden cessation of ongoing activity, the child gives
a blank stare. Within seconds to less than a minute he returns to normal activity with no post
ictal fatigue. Occasionally he may have a few clonic and orobuccal movements. Episodes
may occur innumerable times during the day. It can be induced in your clinic by making
the child hyperventilate for 3 minutes.
44 Algorithms in Pediatric Neurology
Is it myoclonic seizure?
Myoclonic seizures present as a brief, sudden, shock like contraction of the face and trunk or
extremities. They may be part of serious epilepsy syndromes like early myoclonic epileptic
encephalopathy, infantile spasms, Dravet’s syndrome, or progressive myoclonic epilepsy.
Step IV
Look for etiology
A seizure is a symptom not a disease. History, examination and investigations must be care-
fully directed towards hunting for an etiology. We need to look for:
• CNS infections like meningitis if there is fever, neck rigidity or rash,
• CNS trauma if there is a history
• Metabolic disturbances if there is a setting such as diarrhea, vomits, renal failure which
may have cause dyselectrolytemia.
• Intracranial SOL if there is history to suggest raised intracranial tension or unexplained
focal neurological deficit
• Degenerative brain disorder if there is history of regression of milestones
• Inborn errors of metabolism if there is history of recurrent neonatal deaths, unexplained
smells, vomits and lethargy.
Step V
Look for precipitating causes
Fever, sleep deprivation, anxiety, drug noncompliance can all precipitate seizures.
Step VI
Investigations to order
a. EEG: This may be normal in 50% of cases in the interictal period. It helps to differenti-
ate a focal from a generalized seizure. Some patterns are pathognomonic of the type of
epilepsy, e.g. (3/sec spike in absence seizure, hypsarrhythmia in infantile spasms). Video
EEG may be useful to distinguish pseudoseizure from seizure.
b. Neuroimaging: An MRI is usually more useful than a CT head.
The Child with Seizures 45
CT head is useful because of its low cost, speed and availability. It is useful in unstable
patients, when we need to pick up bleeds (e.g. Head trauma, postoperative bleeds, etc.)
and to pick up calcification, e.g. in Sturge-Weber syndrome and tuberous sclerosis).
An MRI brain uses nonionizing radiation, can get images in multiple planes and has
high anatomical resolution. Mesial temporal sclerosis and developmental malformations
(e,g. Focal cortical dysplasias, lissencephaly and polymicrogyria) are picked up better
on MRI.
c. Baseline serum calcium, electrolytes, complete bood counts and aminotransferase may
be useful before starting anti epileptic drugs but are not compulsory.
d. Other investigations to look for etiology need to be tailored according to the particular
patient.
Step VII
When not to start antiepileptic drugs
a. First episode of a generalized tonic clonic seizure in a child with normal milestones,
normal neurological examination and normal neuroimaging.
b. Single seizure with clear cut self limited precipitating event like hypoglycemia, etc.
Step VIII
When to start antiepileptic drugs
a. Two or more seizures
b. First seizure with any two risk factors: family history positive, partial seizures, abnormal
EEG, symptomatic epilepsy and occurrence in sleep.
Step IX
Which antiepileptic to choose
Choice of drug depends on type of seizure or epilepsy syndrome. There are many possible
drugs you may start with depending on age of the patient, his financial status and comorbid
problems. To simplify matters the most commonly useful drug for each type of seizure is
being mentioned:
a. Generalized seizures: Sodium valproate (20-40 mg/kg/day)
b. Partial seizures: Carbamazepine (10-15 mg/kg/d) or oxcarbazepine (10-30 mg/kg/d)
c. Absence seizures: Sodium valproate
d. Myoclonic seizures: Sodium valproate
e. Infantile spasms: Steroids or ACTH, pyridoxine, topiramate, vigabatrin
46 Algorithms in Pediatric Neurology
Step X
What to do when seizures recur despite therapy?
a. Check for any avoidable precipitating factor
b. Confirm drug compliance
c. Check drug levels
d. Check whether really seizure or pseudoseizure
e. Re-evaluate whether you are using the most appropriate drug
f. Increase drug dose
g. Add another drug.
Step XI
When to stop drugs
a. Child should be seizure free for at least 2 years.
b. Longer duration is required if there are risk factors for recurrence such as – underlying
neurological dysfunction (motor deficit, mental retardation), onset < 2 years or >12 years,
numerous seizures before seizure control, abnormal EEG at 2 years.
c. Taper over 3-6 months.
d. Risk of recurrence in the 6 months post stopping is 25% without risk factors and 50%
with risk factors.
Step XII
Special situations: Febrile seizure
a. Typical febrile seizure: The child is between 6 months and 5 years age. He has a fever.
He then has a generalized tonic clonic seizure. It is brief and usually occurs on the first
day of fever. He recovers sensorium very quickly and becomes instantly active. It usu-
ally does not recur in that episode of fever, but can recur in the next episode with fever.
There is often a family history of febrile seizures.
b. Atypical febrile seizure: The febrile seizure is atypical either because (i) it is prolonged,
lasting >15 minutes, (ii) multiple episodes occur in that episode of fever or (iii) it is
partial and not a generalized seizure.
c. Investigations: CSF must be considered in (i) first episode of febrile seizure (ii) a child
< 18 months where meningeal signs may be unreliable (iii) if seizures are complex or
sensorium remains clouded for a longer time than expected.
d. Management: Patients must be reassured and cause of fever must be looked for and
treated. No routine drug is recommended for prophylaxis of typical febrile seizure. In
every repeat episode of fever, parents may be advised (i) antipyretics (ii) tepid sponging
(iii) oral clobazam (0.75 mg/kd/d in dd) for the first 3 days of fever or (iv) oral diazepam
0.3 mg/kg TDS.
The Child with Seizures 47
Step XIII
When to refer for epilepsy surgery
a. Indications: (i) Medically intractable seizures, (ii) seizures significantly reduce quality
of life, (iii) preferably have a localized seizure focus, (iv) there are biological predictors
of seizure persistence
b. Medically intractable seizures are generally defined as those who fail maximally toler-
ated doses of 3 or more antiepileptic drugs either alone or in combination.
c. Presurgical evaluation is done to see whether there is a focal area of seizure focus which
can be safely resected without major consequences. Investigations include video EEG,
invasive EEG with subdural or epidural electrodes, high quality MRI, SPECT or PET
scans, magnetoencephalogram (MEG), and neuropsychological studies.
d. Types of surgical procedures include temporal lobectomy (for temporal lobe seizures),
extratemporal resection, corpus callosotomy, hemispherotomy, subpial transactions.
Step XIV
When to consider ketogenic diet
a. Indications: Medically refractory seizures of all types have been treated with the ke-
togenic diet. It is the treatment of choice in seizures due to glucose transporter defect
and pyruvate dehydrogenase deficiency. It has been used extensively in children with
refractory seizures due to Lennox-Gastaut syndrome.
b. Mechanism: The child is fed a diet with a high proportion of fat. The fat: carbohydrate
+ protein is usually between 3 to 4: 1. Lower ratios have also been used. The brain
starts using ketones predominantly resulting in GABAb shunt activity which is one of
the reasons hypothesized for stopping of seizures. There are considerable difficulties in
maintaining the diet since high fat diet can be very unpalatable. The child is monitored
for weight loss, renal stones, hypoproteinemia. Urine ketones are monitored several
times a day to maintain persistent ketosis for the diet to be effective.
c. Efficacy: One-third to one half of treated children had a ‘‘good’’ or ‘‘excellent’’ response
to the diet, variously defined as at least 50% fewer seizures.
Bibliography
1. Wallace SJ, Farrell K. Epilepsy in children, (2nd edn), 2004.
10
Approach to Movement Disorders
Movement disorders are a diverse bagful of conditions where there is an abnormal type or
speed of various movements. Often they are due to disorders of the basal ganglia and are
called extrapyramidal disorders.
Step I
Decide which movement disorder he has
The best way to recognize a particular type of movement disorder is to have either seen it
before or see it on a video. You could try searching on the internet for some classic videos
of movement disorders.
Approach to Movement Disorders 49
Step II
What is the etiology?
a. First consider drugs: The common drugs we encounter in day to day practice include
antiemetics like metoclopramide which can precipitate a dystonic reaction which responds
well to diphenhydramine (benadryl).
The second commonly implicated drug phenytoin which can cause choreiform move-
ments and dystonia.
Haloperidol often can induce tardive dyskinesia which presents with involuntary movem-
nts of tone, lips, face, extremities. It can also induce bradykinesia, rigidity and pill rolling
tremor.
Other drugs implicated include antipsychotics (resperidone, olanzapine); antidepressants
(fluoxetine, imipramine); anticonvulsants (phenobarbitone, carbamazepine); antimalarials
(chloroquine) and antihistaminics.
b. Next consider infectious or post infectious disorders: Sydenhams chorea is a common
cause of chorea in young children with post streptococcal acute rheumatic fever. Japa-
nese B encephalitis may present with extrapyramidal symptoms in the post encephalitis
stage. PANDAS (postinfectious autoimmune neuropsychiatric disorders associated with
streptococci) has been implicated in chorea, tics, and obsessive compulsive disorders.
c. Next consider static encephalopathies due to structural damage to the basal ganglia.
Kernicterus is an important cause of athetoid cerebral palsy. Stroke in the basal ganglia
region is another.
d. Rule out genetic disorders like Wilsons disease, Huntingtons Chorea, dystonia mus-
culorum deformans, glutaric aciduria and dopa responsive dystonia.
e. Is it a conversion reaction? Look for underlying psychological underpinnings which
may be causing a patient to mimic movement disorders.
50 Algorithms in Pediatric Neurology
Step III
Is it Sydenhams chorea?
a. Clinical features: It starts some months after acute rheumatic fever. The onset is insidi-
ous with 3 cardinal components: Chorea, emotional lability and hypotonia. Examination
findings include a jack in the box tongue, milkmaids grip, pronator sign and spooning
of fingers when extended.
b. Investigations: Diagnosis is of exclusion, since the throat swab may be normal and
Antistreptolysin O antibodies (ASO) is elevated in just 60%. Anti DNAase and anti NA-
Dase are positive much longer than ASO. An ECHO may show evidence of rheumatic
heart disease.
c. Start penicillin prophylaxis. A trial of diazepam for 1-2 days may be tried. If there is no
response use valproate (10-20 mg/kg/d) or haloperidol (0.5-2 mg BD), clonazepam or
carbamazepine may be used.
Step IV
Is it Wilsons disease?
Clinical Features
Onset of symptoms is after 5 years. In younger children hepatic symptoms predominate.
Neurological symptoms usually occur in the adolescent age group. Dystonia, chorea, trem-
ors, rigidity, seizures, mild dementia may all occur. Associated symptoms may include
acute or chronic liver disease, hemolytic anemia, renal tubular dysfunction, arthritis and
hypoparathyroidism.
Diagnosis
Diagnosis is made when:
i. Serum ceruloplasmin is < 200 mg/L and Keiser Fleisher rings are present or
ii. A serum ceruloplasmin < 200 mg/L and copper in liver biopsy > 250 ug/gm dry weight.
24 hour urine copper is usually >100 ug and increase to >1000 ug after a penicillamine
challenge of 500 mg BD over 24 hours. The typical MRI abnormality is increased T2-
weighted signal in the caudate, putamen, subcortical white matter, and/or brainstem.
Treatment
i. Start a low copper diet avoiding nuts and chocolate.
ii. Oral penicillamine is used at 20 mg/kg/day in divided doses 30 minutes before and 2
hours after meals. An effective dose of penicillamine will keep the 24-hr urinary copper
excretion between 200 and 500 mg per day.
Approach to Movement Disorders 51
Step V
General Principles of Management
a. Basic investigations include ASLO, DNAase B titres, blood sugar, s. calcium, ESR,
thyroid function tests, S. ceruloplasmin, ANA and antiphospholipid antibodies. MRI
brain may be useful.
Wilsons disease: Increased T2-weighted signal in the caudate, putamen, subcortical white
matter, and/or brainstem.
Hallervorden spatz disease: Eye of the tiger sign with hypointensity in the globus pal-
lidus on T2
b. Treat the underlying disease (Wilsons-d penicillamine, Sydenhams-penicillin prophy-
laxis).
c. In movement disorders with excessive movements, e.g. Chorea: there appears to be an
excess of dopamine in the basal ganglia circuits. The treatment is to use a dopamine
antagonist like haloperidol (0.5-2 mg BD). Other drugs include valproate
d. For movement disorders with decreased movement where there is a deficiency of
dopamine like Parkinsons—use levodopa (start 1 mg/kg/day, go up to 5 mg/kg/d).
e. In dystonia there is often a deficiency of dopamine. In many childhood dystonias giving
a small dose of dopamine may reduce the dystonia.
f. In dystonia caused by antidopaminergic medications the treatment is to use anticholin-
ergics (e.g. Trihexphenidyl 1-60 mg/day titrate slowly up).
g. Botox: Botulinum neurotoxin has been used as a treatment option for the treatment of
cervical dystonia, blepharospasm, focal upper extremity dystonia, adductor laryngeal
dystonia, upper extremity essential tremor, hemifacial spasm, focal lower limb dystonia,
and motor tics.
h. Deep brain surgery such as stereotactic thalamotomy and pallidotomy has been used to
treat various symptoms of Parkinsons such as tremor, rigidity and dyskinesia.
Bibliography
1. McMahon WM, Filloux FM, Ashworth JC, Jensen J. Movement disorders in children and adolescents.
Neurol Clin N Am 2002;1101-24.
11
The Child with Fever and Encephalopathy
A febrile child who is drowsy is a pediatric emergency. This child can deteriorate rapidly
and die if not managed well. If the diagnosis and management is done rapidly you may save
his life and prevent long term sequelae like epilepsy, deafness and mental retardation. You
need to think systematically while managing this child.
Step I
Is it febrile encephalopathy or fever delirium?
High fever can induce delirium. This is brief and lasts only as long as the temperature is
elevated and is not ominous like other causes of febrile encephalopathy. In febrile encepha-
lopathy the alteration of sensorium lasts for more than 8 hours.
Step II
Is there any metabolic cause of encephalopathy?
If the encephalopathy is not just fever delirium, rule out easily correctable metabolic ab-
normalities.
Blood Sugar
Both low and high blood sugar need urgent attention. Hypoglycemia (whole blood glucose
< 50 mg/dl in a child) due to poor intake in fever may cause drowsiness. A blood sugar
more than 200 mg/dl in the setting of polyuria, polydipsia, dehydration, abdominal pain
must make you suspect diabetes mellitus. Metabolic acidosis with ketonuria in the presence
of hyperglycemia will confirm diabetic ketoacidosis. A urine with both sugar and ketones
is very suggestive of DKA.
Sodium
Both hyponatremia and hypernatremia due to various causes such as gastroenteritis, vomit-
ing, wrong preparation of ORS may cause drowsiness, irritability and seizures.
The Child with Fever and Encephalopathy 53
Step III
Is the illness acute, subacute or chronic?
If you have ruled out metabolic causes of encephalopathy, look for CNS infection.
If illness is acute
Rule out meningitis: If the history is short, there are meningeal signs, anterior fontanelle
is full or the child has purpura suggestive of meningococcemia, perform a lumbar puncture
to rule out meningitis.
Think of encephalitis: If febrile encephalopathy is not associated with meningeal signs,
there is an epidemic going on or there are focal symptoms or signs. Clues for etiology are:
• Aphasia and psychiatric symptoms—herpes encephalitis
• Extrapyramidal signs—Japanese B encephalitis
• Vesicular rash—Varicella
• Parotitis—Mumps
• Hypotension, bleeds, pleural effusion, thrombocytopenia—dengue
• Myocarditis, acute flaccid paralysis—enterovirus.
Think of cerebral malaria: If there are no meningeal signs, symmetrical encephalopathy,
no focal signs, but there may be anemia, thrombocytopenia and splenomegaly. The CSF
will have no cells.
Typhoid fever may be associated with neurological complications like encephalopathy,
motor deficits, ataxia, aphasia, seizure and cranial nerve deficits often in the third week of
fever or even earlier sometimes.
Acute disseminated encephalomyelitis (ADEM) may start with fever, lethargy, vomits.
The child then develops seizures, motor deficits, optic neuritis, coma and myelitis. MRI has
characteristic multifocal, demyelinating, white matter lesions in the brain and spinal cord.
54 Algorithms in Pediatric Neurology
Step IV
Investigations
Lumbar Puncture
It is indicated to confirm the diagnosis of meningitis. Lumbar puncture is contraindicated if
there is respiratory or cardiovascular compromise, evidence of significant raised intracranial
pressure (papilledema, absent pupillary reflexes, motor posturing, drowsy), asymmetrical
neurological signs, recent seizure < 30 minutes, or deep coma.
Neuroimaging
Perform a neuroimaging before lumbar puncture, if there are focal neurological signs,
papilledema, known CNS disease and in immunocompromised patients. A contrast CT head
is usually adequate in most acute conditions especially when patient is unstable. In suba-
cute or chronic conditions an MRI is preferable. Avoid lumbar puncture if CT head shows
(i) midline shift (ii) posterior fossa mass (iii) loss of basilar, suprachiasmatic, superior cer-
ebellar and quadrigeminal cisterns.
Confirmatory Tests
Confirmatory tests in various conditions are as follows:
Pyogenic meningitis: Cerebrospinal fluid (CSF) has cells often in thousands, predominantly
neutrophilic, with elevated proteins and low sugar. Gram stain, antigen detection and culture
may help identify organism.
Encephalitis: Cerebrospinal fluid has cells in tens or hundreds, mainly lymphocytic with
not much change of protein or sugar.
i. CSF PCR may clinch the etiology for herpes, Japanese B.
ii. CSF serology IgM may be positive in herpes virus, Japanese B (sensitivity and specifi-
city > 95%), Dengue (ELISA in CSF and serum).
iii. MRI brain-temporal lobe lesions (herpes), gray matter lesions especially thalamus
(Japanese B), brainstem lesions (enterovirus 71), multiple small white matter lesions
(Nipah virus).
Cerebral malaria: Tests for identifying Falciparum malaria include peripheral smear ex-
amination, fluorescent microscopy and antigen detection.
Typhoid: Blood culture will grow Salmonella typhi.
ADEM: MRI will show multifocal demyelinating lesions in white matter, thalamus and
spinal cord.
56 Algorithms in Pediatric Neurology
Step V
Treatment
Pyogenic Meningitis
• Start IV antibiotics in high antimeningitic doses.
• Age < 2 month: Ceftriaxone (100 mg/kg in 2 dd) or cefotaxime (200 mg/kg in 4 dd) plus
ampicillin (300 mg/kg in 4 dd)
• Age > 2 month: Ceftriaxone (100 mg/kg in 2 dd)
• In patient with a ventriculoperitoneal shunt or resistant Pneumococcus—IV Vancomycin
(60 mg/kg/d in 4 dd).
• IV Dexamethasone 0.15 mg/kg/dose 6 hrly for 4 days is recommended for post-neonatal
meningitis (especially H. influenzae or Pneumococcal) to reduce morbidity.
Encephalitis
The diagnosis of herpes simplex encephalitis (HSE) should be considered in any patient
with a progressively deteriorating level of consciousness, fever, abnormal CSF findings, and
focal neurological abnormalities in the absence of any other causes. IV Acyclovir (10 mg/kg or
500 mg/m2 8 hourly, as infusion over 1 hour for 14-21 days). Supportive care includes reduc-
tion of intracranial hypertension, maintaining airway, breathing and circulation, normalizing
electrolytes and sugar, and antiepileptics.
The Child with Fever and Encephalopathy 57
Cerebral Malaria
Three possible regimens for therapy are:
a
Recommended by WHO in low transmission areas or outside malaria endemic areas.
b
Recommended by WHO for children in high transmission areas; regimen 1 can also be used.
c
For areas where artesunate or artemether are not available, mainly the US. National Vector Borne Disease
Control Program in India recommends quinine as the treatment for severe malaria in pregnancy. Loading
dose should not be administered to patients who received quinine, quinidine, halofantrine, or mefloquine
within the preceding 12 hours.
d
Not for children below 8 years of age and pregnant women
e
Mefloquine has important neuropsychiatric and cardiac adverse effects; not an ideal drug for pregnancy;
cannot be used concomitantly with quinine or quinidine.
Typhoid Encephalopathy
Besides IV antibiotics according to susceptibility like Ceftriaxone, IV dexamethasone
3 mg/kg followed by 1 mg/kg 6 hourly for 24-48 hours reduces mortality in encephalopathy.
ADEM: IV Methylprednisolone 20 mg/kg/day for 3-5 days with oral taper over 3 weeks.
For nonresponders plasmapheresis 3-5 cycles or IVIG 2 g/kg over 2-3 days.
ICSOL: Neurosurgical consult. IV antibiotics for abcess (ceftriaxone + vancomycin+ met-
ronidazole) and steroids to reduce cerebral edema.
58 Algorithms in Pediatric Neurology
CNS vasculitis: For progressive large vessel disease: Monthly pulse cyclophosphamide with
high dose corticosteroid followed by 18 months of azathioprine or mycophenolate mofetil
+ tapering steroids.
For non progressive disease use 3 months of tapering steroids and antiplatelet agents.
Supportive care includes initial low molecular weight heparin and antiplatelet agents,
anticonvulsants and antipsychotics.
Bibliography
1. Bonthius DJ, Karacay B. Meningitis and encephalitis in children: An update. Neurol Clin N Am
2002;20:1013-38.
2. Fredrick Southwick. Central Nervous system Infections. In: Infectious Diseases. A clinical short course
(2nd edn), McGraw Hill, 2007.
12
The Floppy Infant
Step I
Is the baby floppy?
You can recognize the floppy infant by the following observations:
1. The posture is frog like (abducted and externally rotated hips)
2. The traction response: Grasp the hands and pull the infant to sitting position. If there
is more than minimal head lag and failure to counter traction by flexion of the limbs it
indicates hypotonia.
3. Vertical suspension: Place both hands in the infants axilla and lift straight up. A floppy
baby will slip through.
4. Horizontal suspension: When suspended prone horizontally a floppy baby forms an
inverted “U”.
Step II
Is it central or peripheral in etiology?
Floppy babies with central pathology may have the following clinical clues:
1. Abnormalities of other brain function like encephalopathy, cognitive delay, seizures.
2. Dysmorphic facies
3. Brisk deep tendon reflexes, sustained ankle clonus, upgoing plantars
4. Microcephaly
5. Malformations of other organs
6. Fisting
7. Scissoring of lower limbs especially when held up.
Floppies with peripheral or lower motor neuron lesions may have the following features:
1. Alert and age appropriate cognitive functions
2. Absent or depressed deep tendon reflexes
60 Algorithms in Pediatric Neurology
3. Tongue fasciculations
4. Muscle atrophy
5. Normal head circumference
6. Low pitched weak cry, poor cough
7. Paradoxical chest wall movements
Step III
If it is central in etiology what can it be?
Pathologies of the central nervous system which may present as floppy baby:
• Static encephalopathies
– Hypotonic cerebral palsy
– CNS malformations
• Genetic disorders
– Trisomy 21
– Prader-Willi syndrome
– Familial dysautonomia
– Lowes syndrome (cerebrohepatorenal syndrome)
• Peroxisomal disorders
– Zellweger syndrome
• Spinal cord defects
– Spinal dysraphism
– Spinal cord injury
Pathologies of lower motor neuron type which may present as floppy infant (Fig. 12.1):
• Anterior horn cell disorders
– Spinomuscular atrophy (SMA)
• Neuropathies
– Congenital hypomyelinating neuropathy
• Neuromuscular junction abnormalities
– Congenital myasthenia
– Transitory neonatal myasthenia
• Muscle disorders
– Congenital myopathy
– Congenital muscular dystrophy
– Congenital myotonic dystrophy
– Metabolic myopathy (Pompe’s disease)
– Endocrine myopathy (hypothyroidism)
– Energy depletion states (mitochondrial, creatinine deficiency, fatty acid oxidation
defects)
The Floppy Infant 61
Step IV
Central causes of a floppy baby
Disease Clinical clues Tests
Hypotonic CP Microcephaly, nonprogressive delay in milestones MRI brain
with brisk jerks.
CNS malformations Dysmorphism, other organ malformations MRI brain
Zellwegers syndrome Dysmorphic facies, pear shaped head, refractory Blood levels of Very
seizures, biliary cirrhosis, polycystic kidneys, CNS long chain fatty acids
malformations, retinal degeneration. (VLCFA)
Prader-Willi syndrome Feeding difficulties at birth, small hands and feet, FISH methylation
almond eyes, later obesity, hypogonadism and studies
mental retardation.
Trisomy 21 Downs facies, simian crease Karyotype
Familial dysautonomia No tears, temperature instability, absent corneal, Supersensitive miosis to
absent fungiform pappilae on tongue. 0.1% pilocarpine
Lowes syndrome Congenital cataract, glaucoma, renal tubular Clinical
acidosis, developmental delay.
Step V
Principles of Management
General
a. Prevent contractures by regular range of movement exercises.
b. Facilitate activities of daily living by occupational therapy.
c. Early treatment of respiratory tract infections.
d. Nasogastric feeding. But avoid obesity.
e. Monitor for hip dislocation and scoliosis.
f. Counsel regarding recurrence risks in next pregnancy.
g. Special precautions during anesthesia. Avoid muscle relaxants. Malignant hyperthermia
may be precipitated in some disorders like central core disease.
Specific
a. Myasthenia: Neostigmine (orally 0.4 mg/kg or IM 0.04 mg/kg 4-6 hrly) or pyridostigmine
(4 times the dose).
b. Congenital hypomyelinating neuropathy: Oral prednisolone 2 mg/kg for 4 weeks then
taper to 0.5 mg/kg alternate day for 1 year.
c. Spinal muscular atrophy: Trials with riluzole (107 mg/m2/day) have shown minor im-
provement.
d. Creatinine deficiency: Supplement with creatinine 50-100 mg/kg/day
Bibliography
1. Dawn E. Peredo, Mark C Hannibal. The Floppy Infant. Evaluation of Hypotonia. Pediatrics in Review
2009;30:e66-e76.
13
A Child with Muscle Weakness
Step I
Is there muscle weakness?
A child with acute muscle weakness may present with varying symptoms. He may present
with ataxia, neck flop, inability to sit or stand, difficulty in feeding or swallowing, shallow
respiration, diplopia or squint.
A child with slowly progressive weakness may present with a history of frequent falls,
toe walking, failure to gain motor milestones or loss of motor milestones, loose or flabby
muscles.
Examine the child in a comfortable environment. Watch him feed, sit, stand up from sit-
ting, walk and play. The quality of his movements will tell a lot about his muscle strength.
The Gowers sign is typically seen in Duchene muscular dystrophy (DMD). When asked
to stand up from sitting position, the child uses his hands to walk up his body.
Toe walking may be an initial sign of DMD.
Check to see whether there is pain and tenderness of muscles or not.
Step II
Is it acute or chronic?
Acute muscle weakness is one which has started in the last couple of hours or days.
Chronic muscle weakness has been going on for several weeks, months or years. Sometimes
the onset is from birth with a history of breech delivery and delayed motor milestones.
Step III
In acute muscle weakness: where is the localization?
A child with a relatively recent onset symmetrical, generalized muscle weakness must make
you think of the following causes.
A Child with Muscle Weakness 65
Central
Causes like acute demyelinating encephalomyelitis (ADEM) or pontine infarcts will have
clues of central involvement in the form of drowsiness, spasticity or brisk jerks. Spinal cord
disease may have a sensory level or bladder involvement in the form of urinary retention.
Peripheral Causes
The localization can be either at the anterior horn cell, radiculopathy, neuropathy, neuromus-
cular junction or muscle.
Diptheritic polyneuropathy Preceding membrane in throat, bull neck, Throat swab may grow
followed by palatal palsy 1-2 weeks later, diphtheria. CSF elevated
blurring of vision due to ciliary muscle proteins, minimal
involvement, multiple cranial nerve pleocytosis, NCV – slow
involvement (V,VII, IX, X), after 5-8 weeks velocities.
descending symmetrical sensory and motor
weakness, progression upto several weeks
and then complete recovery over weeks
if patient survives cardiomyopathy and
respiratory muscle paralysis.
Myasthenia gravis Diurnal variation in muscle weakness, ptosis, Neostigmine test,
opthalmoplegia, bulbar symptoms like repetitive EMG shows
dysphagia, fatigue of muscles on prolonged decremental response,
exercise acetyl choline receptor
antibodies (+ve in 74%).
Botulism Onset in 12-36 hours of contaminated food, CSF normal, EMG shows
nausea vomits, initial symptoms of blurred incremental response with
vision and diplopia, bulbar involvement, repetitive stimulation
unreactive pupils distinguish it from
myasthenia, descending paralysis, severe
constipation, intact sensorium, recovery after
weeks
Organophosphorus Nicotinic symptoms: Fasciculations, weakness, Diagnosis is clinical,
poisoning seizures, anxiety, coma. plasma cholinesterase
Muscarinic symptoms: Bradycardia, miosis, levels not readily
salivation, diarrhea, urination, bronchospasm available.
Hypokalemic periodic Early morning weakness, h/o physical Fall in serum potassium
paralysis exertion or high carbohydrate intake previous during episode (may be
day, weakness lasts hours to 1 week, typically within normal range),
72 hours, intact sensations. EMG – provocative tests
with cooling, exercise and
glucose.
Myositis Symmetrical proximal muscle weakness, Elevated creatine kinase
tender muscles, preceding viral infection,
rash, arthralgias in case of dermatomyositis.
Porphyria Motor neuropathy, severe abdominal pain, Increased urinary
psychiatric behaviour, seizures, coma porphobilinogen
Transverse myelitis Sensory level, bladder involvement MRI spine
Pontine lesion Multiple cranial nerve deficits MRI brain
ADEM Drowsiness, seizures MRI brain
Step IV
Acute muscle weakness: What are the common patterns?
1. Ascending symmetrical paralysis with absent jerks: acute polyneuropathy (e.g. GBS)
2. Symmetrical proximal weakness with intact jerks: acute muscle disease (e.g. myositis,
hypokalemia)
A Child with Muscle Weakness 67
Step V
How to Manage?
Supportive Therapy
1. Maintain ABC’s
2. Intubate if hypoxic, rapidly increasing muscle weakness, risk of aspiration, poor or weak
cough, forced vital capacity by spirometer (FVC) <15 ml/kg.
3. Tube feeds if bulbar symptoms are predominant.
Step VI
In chronic muscle weakness where is the localization?
SMA—Spinal muscular atrophy is a anterior horn cell disease with predominant proximal involvement.
MD—Myotonic dystrophy and EDS—Emery-Dreiyfuss syndrome are muscle diseases with predominant distal
involvement.
A Child with Muscle Weakness 69
Step VII
What is the possible etiology and how to confirm?
Progressive proximal muscle weakness
Neuropathies
Disease Clinical clues Tests
SMA III AR, Distal weakness and wasting, NCV – normal, CPK mild↑, muscle biopsy
preserved reflexes, fasciculations, onset denervation
late childhood
HMSN AD, distal weakness, sensory loss, NCV -↓velocity, sural nerve biopsy , EMG
reflexes ↓, pes cavus, thickened nerves denervation potentials, DNA tests for some
types
Step VIII
How to Manage?
Supportive Management
1. Physiotherapy and braces to prevent contractures.
2. Nasogastric feeds when associated dysphagia.
3. Prevention of injuries to feet.
4. Counseling for next pregnancy.
A Child with Muscle Weakness 71
Specific Treatment
1. Duchene muscular dystrophy: No curative treatment. Prednisolone 0.75 mg/kg/day or
deflazacort 0.9 mg/kg/day has been shown to delay progression. For excessive weight
gain (>20% normal)on prednisolone dose may be reduced to 0.5 or later to 0.3 mg/kg/
day.
2. Polymyositis: Prednisolone 2 mg/kg/day with slow taper over several months and low
dose alternate day for 2 years. IVIG and plasmapheresis in emergencies. Methotrexate
for non responders.
3. Myasthenia: Discussed earlier in this chapter.
Bibliography
1. Jackson CE. A clinical approach to muscle diseases. Semin Neurol 2008;28:228-40.
2. Practice parameter: Corticosteroid treatment of Duchenne dystrophy: Report of the Quality Standards
Subcommittee of the American Academy of Neurology and the Practice Committee of the Child Neurol-
ogy Society. Neurol 2005; 64:13-20.
Index