Ghai Essential Pediatrics8th

to 0.5 cm. This physiological separation disappears after the first fortnight of life. Persistent widening of squamo­ parietal sutures is not physiological and should arouse suspicion of hydrocephalus.

Cranial ultrasound and computed tomography help to evaluate serial ventricular size while the latter gives information aboutcorticalmantle,periventricularoozeand etiology of hydrocephalus. MRI may be necessary to deter­ minethesiteofobstructionandincongenitalhydrocephalus to identify associated malformations. Arnold-Chiari mal­ formation has downward displacement of cerebellum and medulla, obstruction of CSF pathway or migration defects. Dandy-Walkermalformationrevealsacysticmalformation, atresia of outlet foramina or any brain malformations.

Differential diagnosis

Megalencephaly refers to the increase in volume of brain parenchyma. There are no signs of increased intracranial pressure. The ventricles areneitherlarge, norunder increa­ sed pressure. Causes include Hurler syndrome, meta­ chromatic leukodystrophy and Tay-Sachs disease.

Chronic subdural hematoma causes large head, mostly located in the parietal region without prominent scalp veins or sunset sign. Large head size is also observed in hydranencephaly, rickets, achondroplasia, hemolytic anemia and familial macrocephaly.

Treatment Management includes making a precise etio­ logical diagnosis and identification of associated malfor­ mations, clinical course and severity of hydrocephalus.

If hydrocephalus is arrested spontaneously, surgical intervention may not be necessary. Medical management should be instituted if surgery is not indicated. Acetazo­ lamide at a dose of 25-100 mg/kg/day diminishes CSF production in mild, slowly progressive hydrocephalus. Oral glycerol has also been used for similar purpose. A conservative approach is better in most cases.

Iftheheadsizeenlargesrapidly,orisassociatedwithpro­ gressive symptoms, where vision or life is endangeredit is desirable to treat surgically before irreparable damage occurs.In congenital obstructive hydrocephalus, acquired hydrocephalus, periventricular ooze with hydrocephalus

aventriculoatrialorpreferablyaventriculoperitonealshunt shouldbedonetodraintheCSFdirectlyinto thecirculation or into the peritoneal cavity. Third ventriculotomy by endoscopicapproachisanotheroptionparticularlyinchildren with obstructive hydrocephalus. In cases of bacterial meningitis,anacute hydrocephalusmaysetin whichisself limited. Patients with tuberculous meningitis and pro­ gressive hydrocephalus require a shunt, specially if it is obstructive.

A variety of shunts are now available. It is usually necessary to keep theshunt for the entirelife. As the child grows in size it may be necessary to revise the shunt, using

alonger tube. Blockage and infection are the two most common shunt complications. Shunt revision may also be necessary if there is bacterial colonization of the shunt.

Central Nervous System -

Prognosis Even with the best of treatment, prognosis is guarded. Almost two-thirds patients have variable mental and developmental disabilities. Prognosis of hydro­ cephalus associated with spina bifida is not satisfactory.

Pseudotumor Cerebri

It is abenignselflimiting disorderwithgenerallyafavorable outcome. Intracranial pressure is elevated and ventricular systemiseithernormalorsmall. Generally, thereareno focal neurological signs. Onset of symptoms of raised intracranial pressure may be sudden or gradual extending over a week. Visual field shows enlargement of blind spot.

Pseudotumor cerebri may follow use of outdated tetracycline,highdosesofvitaminA,quinolones,lateralsinus thrombosis (following otitismedia,mastoiditis especially on the right side) and obstruction of venous outflow due to pressure on superior vena cava. It may occur during withdrawal of corticosteroid therapy, Addison disease, hypoparathyroidism and systemic lupus erythematosus. EEGshowsexcessiveslowwaveactivity.Isotopebrainscan, CT or MRI arenormal. Thepatientimproves spontaneously after a few months. Acetazolarnide or oral glycerol helps in symptomatic relief. Dexamethasone may be required. Cerebral decompression is rarely necessary.

Suggested Reading

Duhaime AC. Evaluation and management of shunt infections in children with hydrocephalus. Clin Pediatr (Phila) 2006;45:705-13

Matthews YY. Drugs used in childhood idiopathic or benign intracranial hypertension. Arch Dis Child Educ Pract Ed 2008;93:19-25

NEURAL TUBE DEFECTS

Neural tube defects (NTD) are one of the most common congenital anomalies due to failure of proper closure of neural tube and covering mesoderm and ectoderm. These defects occur in about 1.5 per 1,000 live births; the risk in second sibling is 5 per 100 births. The incidence in North India is as high as 3.9-9/1,000 live births.

Etiology

Primary neural tube defects have multifactorial inheri­ tance. Maternal risk factors include zinc and folate defici­ ency,alcohol,radiationexposure,insulindependentdiabe­ tes mellitus (IDDM), and use of valproate and carbama­ zepineduringpregnancy. Patients with trisomy 13 and 15 shows these defects.

Maternal folatedeficiencyis an importantrisk factor for development of NTD. Periconceptional folic acid supple­ mentation with 4 mg folate supplementation 1 month beforeconceptionandthroughfirsttrimester decreases the occurrence and recurrence of NTD. The exact mechanism for this protective effect remains unknown.

Clinical Features

The defect is obvious at birth or through fetal sonography. It varies in severity from an occult anomaly to severe life-

threateningproblem. Lumbosacralregionisthe commonest site, but any part of the spine may be affected. The defect may extend over a variable length of the spinal cord.

The spectrum includes spina bifida (meningocele, meningomyelocele, spina bifida occulta), anencephaly (absence of brain calvaria, total or partial), encephalocele (herniation of brain and meninges through defect in calvaria), craniorhachischisis (anencephaly associated with continuous bony defect of spine and exposure of neural tissue) and iniencephaly (dysraphism of occipital region accompanied by retroflexion of neck and trunk).

Neural tube defects may be associated with other congenital anomalies and dysfunction of organ systems. Affected children may have lower body paralysis, bladder and bowel dysfunction, learning disabilities, hydrocephalus due to Arnold-Chiari type 2 malfor­ mation and endocrine abnormalities. Anencephaly is an important cause of fetaland infant mortality. Severe cases die in utero, or in the early neonatal period. Longterm sequelae includeneurological, motor,physicaldisability, psychosocial maladjustments and increased financial burden on family.

Spina bifida occulta constitutes about 5% cases and is asymptomatic. Meningocele or myelomeningocele, presents clinically as a raw red fleshy plaque, consists of meninges, CSF, nerve roots and dysplastic spinal cord. In meningocele, the sac is covered only by skin and generally there is no neurologic deficit.

In meningomyelocele the neurologic deficit includes varying degrees of flaccid paraparesis and sensory deficit in the trunk and legs corresponding to involved segments of the dysplastic cord. The cord distal to the site of the lesion is severely affected. Involvement of bowel and bladder results in fecal and urinary incontinence. Hydrocephalus is usually present in varying degrees. Arnold-Chiari malformation may cause facial weakness and swallowing difficulty. Tongue movements may be impaired and there may be laryngeal stridor.

Management

Prenataldiagnosis ofmyelodysplasia ispossiblebyelevated alpha-fetoprotein level in the maternal blood between 14 and 16 weeks of gestation, or in the amniotic fluid in early pregnancy where the test is more specific. Additional test in amniotic fluid includes acetyl cholinesterase estimation. Ultrasound detection is around 100%; raised maternal blood alphafetoprotein has accuracy of 60-70%, amnio­ centesis for alpha-fetoprotein and acetylcholinesterase has accuracy of 97%.

urologist and orthopedic surgeon with assistance from physiotherapist, social worker and psychiatrist. The degree of paralysis, presence of hydrocephalus, kyphosis, congenitalmalformation, evidence of infection of nervous system influences decisions.

Surgery includes closure of the defect and a VP shunt (if associated with hydrocephalus). Early closure prevents neurological deterioration. Open lesions draining CSF should be closed within 24 hr. Closed lesions should be operated within 48 hr.

Lorber's criteriafor selective surgery. Surgery is not recom­ mended if there is severe paraplegia at or below L3 level, kyphosis or scoliosis, gross hydrocephalus, associated grosscongenital anomalies, intracerebralbirth injuries and neonatal ventriculitis before closure of back.

Prognossi

Delay ininterventioncauses increase incomplicationslike worsening of neurologic deficit, infection (local or ventriculitis) and progressive hydrocephalus. Late complications include: hydrocephalus in 80-90% because of Chiari II malformation, urinary tract infections, enure­ sis, fecal incontinence or constipation, sexual dysfunction, intellectual deterioration, delayed neurological problems (tethered cord, intradural mass lesions), epilepsy in 10-30%, ocular problems (30%), shunt infection (25%), psychosocialproblems and motor deficits. 2% die during initial hospitalization and 15% die by ten years of age.

Prevention

Primary prevention includes periconceptional folate supplementation to all prospective mothers. Food fortification is another possible approach. Counseling of family with a previous child with NTD is essential. The risk of recurrence is 3.5% with 1 affected child, 10% with 2 affected children and 25% with 3 affected children. MTHFR polymorphisms should be studied in case of recurrence of birthswithNTD.Periconceptionalfolate and prenatal diagnosis is advised in subsequent pregnancy. Folate supplementation reduces recurrence risk by 70%. Zinc and vitamin A supplementation is also advised.

Dose forprimaryprevention is0.4mg per day. A mother who has previously delivered a child with NTD should receive 4 mg per day of folic acid in subsequent preg­ nancies. Secondaryprevention is imperativeafteranindex case. Duration of supplementation is 2 monthsbefore and 3 months after conception.

Investigationsincludeultrasound ofhead, meningocele and the abdomen and chest and spine X-rays.

Treatmen t

Management of NTD requires a team approach with the cooperation of pediatrician, neurologist, neurosurgeon,

SuggestedReadngi

Birnbacher R, Messerschmidt AM, Pollak AP. Diagnosis and prevention of neural tube defects. Curr Opin Urol 2002;12:461-4

Kibar Z, Capra V, Gros P. Toward understanding the genetic basis of neural tube defects. Clin Genet 2007;71:295-310

Pitkin RM. Folate and neural tube defects. Am J Clin Nutr 2007; 85: 285S-8S

Shaer CM, Chescheir N, Schulkin J. Myelomeningocele: a review of the epidemiology, genetics, risk factors for conception, prenatal diagnosis and prognosis for affected individuals. Obstet Gynecol Surv 2007;62:471-9

ACUTE HEMIPLEGIA OF-------------CHILDHOOD

Acute hemiplegia of childhood is most often due to cere­ brovascular disorders. The exact cause often remains obscure despite extensive biochemical and radiological investigations.

Causes

Cerebral venous sinus thrombosis. Inherited prothrombotic conditions (deficiency of antithrombin III, protein C or protein S; factor V Leiden mutation; homocysteinemia); acquired prothrombotic condition (nephrotic syndrome, antiphospholipid antibodies); infections (otitis media, mastoiditis, sinusitis, meningitis); systemic lupus erythematosus; polycythemia, thrombocytosis; head trauma; neurosurgery dehydration

Arterial thrombosis or embolism. Cyanotic congenital heart disease;infectiveendocarditis;paradoxicalembolithrough patent foramen ovale; arrhythmia; sickle cell SS or SC disease;polycythemia; thrombocytopenia;thrombocytosis antiphospholipid antibodies; inherited prothrombotic conditions (as listed above); disseminated intravascular coagulation;paroxysmalnocturnalhemoglobinuria;infec­ tions (meningitis, bacteremia, local head and neck infections); systemic lupus erythematosus; head trauma

Intracranial hemorrhage. Arteriovenous malformation; cerebral aneurysm; coagulopathy; inherited or acquired thrombocytopenia; thrombasthenia

Infections. Cerebral abscess, meningitis, encephalitis

Intracranial spaceoccupyinglesion. Cerebral tumor (primary or metastatic); inflammatory granuloma

Focal postviral encephalitis. Herpes virus, varicella

Moyamoya syndrome

Transient cerebral arteriopathy. Vascular spasm; drug induced (amphetamine, cocaine), metabolic disease with stroke like episodes (MELAS, Leigh disease, homocysti­ nuria, pyruvate dehydrogenase deficiency, ornithine transcarbamoyl transferase deficiency); intracranial vas­ cular dissection

Todd paralysis

Porencephaly

Clinical Features

Mode ofonset. The rapidity of onset varies with the cause. Emboli occur abruptly with maximum neurological signs at onset and improves with time. Although intracranial

Central Nervous System -

hemorrhageoccursacutely,itmanifestsusuallyaftera brief lapse with headache and nuchal rigidity. Cerebrovascular thrombosis is relatively less rapid in onset.

History and physical examination. History of ear, throat mastoid infection, intraoral or neck trauma, associated cardiacdiseaseorhematologicaldisorders may be helpful in determining the cause.

In mild hemiparesis, one should observe for circum­ duction of involved leg, asymmetric movements of upper extremities and cortical fisting of involved hands. If the child is pushed from sitting position the child extends his arm to protect himself from a fall, called lateral propping reaction. In spastichemiplegia, thisreactionis asymmetric. Absent propping reaction in infants after the age 8-9 months is always abnormal.

Benign intracranial hypertension occurs in lateral sinus thrombosis. Seizures, raised intracranial pressure and vomiting are common in superior sagittal sinus throm­ bosis. Arterial occlusions generally occur in the first two years of life. These may be associated with hemiparesis and seizures, which are difficult to control with medi­ cation. Hemiparesis, cerebral hemiatrophy and cerebral porencephaly may result.

Localization

Cortical lesions. Cortical lesions are characterized by the specificpattern of motordeficit,depending on the vascular distribution of the artery involved. Seizures and cortical sensory loss are usual.

In the left-sided lesion, aphasia is a dominant clinical feature. The child has difficulty in reading, writing and comprehension. Organization of space and body image are affected. In right parietal lesions, the child exhibits lack of attention for objects on his left side. He may ignore the left side of a picture placed before him or may not even recognize his left hand. He has difficulty in copying simplefigures, (indicatingconstructionalapraxia). He gets lost easily and confuses directions given to him because of spatial disorganization.

Corona radiata. The hemiplegia is generally complete and seizures are absent.

Internal capsule. Hemiplegia is complete, often with sensory loss.

Midbrain. Hemiplegia affects the contralateral side and paralysis of 3rd and 4th cranial nerves on the same side (Weber syndrome).

Pons. Hemiplegia affects the opposite side and involves paralytic of 6th and 7th cranial nerves on the same side (Millard-Gubler syndrome).

Medulla oblongata.Contralateralhemiplegia with ipsilateral involvement of lower cranial nerves is noted.

Management

Investigations for the predisposing illness should include platelet count, hemoglobin, MCV, MCH, serum iron and iron binding capacity, nitroprusside reaction for homo­ cystinuria,sicklecellpreparationof blood,antinuclearanti­ body tests, protein C and S estimation, Factor V Leiden, testing for MTHFR mutations, antiphospholipid anti­ bodies, serum and CSF lactate and pyruvate, chest X-ray and echocardiography. Metabolic tests are done if indi­ cated. Investigations should include CT scan, electro­ encephalogramandMRangiography. Lumbarpunctureis indicated if an inflammatory CNS disease is suspected.

Treatment. Specific treatment depends on the etiology of hemiplegia. The role of tissue plasrninogen activator in childhood stroke is not established. In thrombotic stroke, low molecular weight heparin may be indicated followed by oral warfarin pending evaluation for underlying prothrombotic state. Seizures should be controlled and hydration should be maintained. Physiotherapy and speech therapy should be started early.

Treatmentofacutecerebralthrombosisisdirectedtowards increasing cerebral perfusion, limiting brain edema, and preventingrecurrences. Aspirinmaybeindicatedtoprevent recurrence. Calcium channel blockers have been found useful in some. Seizures oftenpersist and anticonvulsants may be required.

Prognosis

Prognosis with regard to seizures and mental retardation is worse in acute idiopathic hemiplegia below 3 yr of age. Herniplegic side may be atrophied and athetosis may be seen on the same side. Cerebralherniatrophy with flatten­ ing of the skull and porencephaly secondary to paren­ chymal damage may occur.

Suggested Reading

Bernard TJ,GoldenbergNA. Pediatric arterial ischemic stroke. Pediatr Clin North Am 2008;55:323-38

Carpenter J, Tsuchida T. Cerebral sinovenous thrombosis in children. Curr Neurol Neurosci Rep 2007;7:139-46

Carpenter J, Tsuchida T, Lynch JK. Treatment of arterial ischemic stroke in children. Expert Rev Neurother 2007;7:383-92

Jordan LC, Hillis AE. Hemorrhagic stroke in children.Pediatr Neurol 2007;36:73-80

Mackay MT, Monagle P. Perinatal and early childhood stroke and thrombophilia. Pathology 2008;40:116-23

Nelson KB, Lynch JK. Stroke in newborn infants.Lancet Neurol 2004;3:150-8

Seidman C, Kirkham F, Pavlakis S. Pediatric stroke: current developments. Curr Opin Pediatr 2007;19:657-62

PARAPLEGIA AND QUADRIPLEGIA

Paraplegia refers to motor weakness of both lower limbs. Quadriplegia is the nomenclature used for neurological weakness of all four limbs; theinvolvementis more in the upper limbs as comparedto the lower extremities. Neuro­ logical weaknessmaybe (i) spastic with spasticity, exagge-

rated tendon reflexes and extensor plantars; or (ii)flaccid with flaccidity, diminished tendon reflexes, flexor plantar response and musclewasting. It may be acute or insidious in onset and have a variable course. Vascular, traumatic and postinfective lesions are usually acute in onset with variable gradual recovery. Compressive or neoplastic lesions have insidious onset with gradually progressive deficit. Degenerative disorders have an insidious onset with slowly progressive course.

Flaccid weakness may result from involvement of anterior horn cell, nerve roots, nerves and myopathies. Acuteonsetfollows demyelinating polyneuropathy, polio, vascular and traumatic spinal cordinsults. Chronic causes include spinalmuscular atrophy, peripheral neuropathies and myopathies. Table 18.9 enlists the common causes of paraplegia and quadriplegia.

Table 18.9: Causes of paraplegia or quadriplegia Spastic

Compressive

Tuberculosis of spine with or without paraspinal abscess

Extradural, e.g. metastasis from neuroblastoma, leukemia, lymphoma; inflammatory process, such as epidural abscess (usually posterior to the spinal cord), bony abnormalities such asachondroplasia,Morquiodisease,hemivertebraeand occipitalization of atlas vertebra, atlantoaxial dislocation Intradural. Neurofibroma and dermoid cyst Intramedullary. Glioma, ependymoma, hematoor hydro­ myelia

Noncompressive myelopathies

Vascular anomalies of the spinal cord: Arteriovenous malformations, hemangiomas and telengiectasia

Trauma or transection of cord

Transversemyelitis/myelopathy. Viral,neuromyelitisoptica, segmental necrosis due to vascular occlusion, e.g. of anterior spinal artery

Familial spastic paraplegia

Lathyrism due to consumption of Lathyrus sativum Degenerative spinal cord disease

Supra-cord lesions

Cerebral palsy Hydrocephalus Bilateral cortical disease

Bilateral white matter disease

Flaccid weakness

Spinal shock in the initial stages of spinal cord damage, e.g. after trauma, vascular, inflammatory, neoplastic lesions, or transverse myelopathy

Guillain-Barre syndrome Acute poliomyelitis Spinal muscular atrophies Peripheral neuropathies

Botulism, Riley Day syndrome

Pseudoparalysis

Surgery, osteomyelitis, fractures, myositis, metabolic myopathy

It should be remembered that symmetrically brisk tendon reflexes with flexorplantar response may be nor­ mal in children and do not necessarily indicate any patho­ logical process. In case of doubt between plantar reflex and withdrawal response, the dorsilateral aspect of the foot should be stroked (Chaddock maneuver) to obtain the plantar response. In lesions above the level of midbrain, jaw reflex becomes brisk. Abdominal reflexes should be elicited by stroking the skin over the abdomen close to the umbilicus. The patient should be examined carefully for sensory involvement, sensory level, wasting at the segments of the lesion, posterior column involve­ ment and bladder bowel involvement.

Management

In acute myelitis, dexamethasone in high dose (5 mg/kg/ day) or IV methylprednisolone pulse (30 mg/kg/day) for 3-5 days may be useful. Tuberculosis is managed with antitubercular drugs, corticosteroids and local manage­ ment. In acute trauma and paraplegia due to neoplasia, the treatment may be surgical.

Paraplegia is initially flaccid but later becomes spastic with development of painful flexor spasms due to the stimulation of pain fibers. Nursing on foam mattress and frequent change of position on bed would prevent decubi­ tus ulcers. Physiotherapy should be done. Bladder must be emptied regularly by compression or repeated cathe­ terization to prevent it being distended and becoming atonic. Later, the bladder may become spastic with frequent but partial reflex emptying. Urinary tract infection may supervene due to inadequate drainage of the bladder. It should be appropriately treated. In severe spasticity, drugs that reduce tone provide relief.

Guillain-Barre Syndrome

See Chapter 19

SYDENHAM CHOREA (RHEUMATIC CHOREA)

Choreiform movements are irregular, nonrepetitive, quasi­ purposive and involuntary movements that are usually proximal but may affect fingers, hands, extremities and face. Chorea may precede or follow manifestations of rheumatic fever. There is a significant epidemiological association of chorea with rheumatic fever. Nearly one­ third of these patients develop rheumatic valvular heart disease. Concurrent association of chorea with rheumatic polyarthritis is rare because chorea generally supervenes later in the course of rheumatic activity. Chorea is a major criterion for the diagnosis of rheumatic activity.

Clinical Features

Sydenham chorea is more common in girls than in boys. The usual age of onset is 5 to 15 yr. The clinical picture may be variable depending on the severity of the illness.

Central Nervous System -

The child may appear clumsy, and develop deterioration in handwriting. Movements may be limited to one side of the body as in hemiballismus. The movements are aggravated by attention, stress or excitement, but disappear during sleep. Emotional !ability, hypotoniaand a jerky speech are common associations.

Thefollowing clinicalmaneuvers are helpfulin arriving at the diagnosis:

i.When the hand is outstretched above the head, forearms tend to pronate

ii.When hands are stretched forwards, wrist flexes and fingers hyperextend

iii.The childrelaxes hand grip on and off asif he ismilking a cow (Milkmaid grip)

iv.The child cannot maintain tongue protrusion (darting tongue)

v.During speech an audible click is heard

vi.The knee reflex may show a sustained contraction resulting in a hung up reflex.

Investigations. The neurological investigations are gene­ rally unrewarding. Antistreptolysin O titer may not be elevated because the onset of chorea is late.

Prognosis. The disorder is generally self limiting and may last from afew weeks to few months (up to 2 yr). Relapses or recurrences can occur.

Treatment. The child should be protected from injury; bedding should be well padded. These children may be treated with chlorpromazine, haloperidol, sodium valproate or carbamazepine. Drugs are maintained at minimum doses requiredfor symptom suppression. Anti­ streptococcal prophylaxis with penicillin G should be given to prevent recurrence of rheumatic activity.

Suggested Reading

Mink JW. Paroxysmal dyskinesias. Curr Opin Pediatr 2007;19: 652--6 Pavone P, Parano E, Rizzo R, Trifiletti RR. Autoimmune neuro­ psychiatric disorders associated with streptococcal infection: Sydenham chorea, PANDAS and PANDAS variants. J Child Neurol 2006;21:727-36 Weiner SG, Normandin PA. Sydenham chorea: a case report and

review of the literature. J Pediatr Emerg Care 2007;23:20-4

ATAXIA

Ataxia is not unusual in childhood. Movements of the limbsare uncoordinatedevenin absence of weakness. The child is unsteady and tends to sway while standing with feet together. Nystagmus, dysarthria, posterior column signs and evidence of labyrinthine or cerebellar disease or raised intracranial pressure should be looked for. A history of drug, toxins and recent infections is important.

Acute Cerebellar Ataxia

Acute cerebellar ataxia may result from many causes: the common being postinfectious cerebellitis (varicella), drugs; brainstem encephalitis and paraneoplastic states.

Other causes include Miller Fisher syndrome, trauma, migraine, kawasaki disease and inherited episodic ataxia.

The usual age of onset is between 1 and 5 yr. Ataxia may develop within a few hr following a febrile illness. The patient has hypotonia, dysarthria, significant ataxia of gait and some incoordination inextremities. The tendon jerks are often pendular and nystagmus is common. The cerebrospinal fluid shows mild pleocytosis. Prognosis is good. Corticosteroids are useful and a quick response is observed. Recurrence is uncommon. Postviral ataxia is an diagnosis of exclusion; other diagnoses should be entertained if ataxia recurs or does not respond.

Ataxia-Telangiectasia

This is an autosomal recessive disorder localized to long arm of chromosome 11, characterized by progressive cerebellar ataxia starting at 1-3 yr. A few years later, telangiectasia over the conjunctivae and skin may be observed. These children may have IgA deficiency or impaired cell mediated immunity, frequent sinopulmonary infections and increased predisposition to lymphoreticular malignancies. They have elevated alpha-fetoprotein levels and defects in DNA repair.

Friedreich Ataxia

This autosomal recessive disorder presents inadolescence or second decade. The classical changes include degene­ ration of the dorsal,pyramidal and spinocerebellar spinal tracts.

Thereislossofpositionandvibrationsense,ataxianysta­ gmus,dysarthriaandareflexia. Plantarresponseisusually extensorbecauseofpyramidalinvolvement. Intellectisnot affected. In addition, these children show skeletal abnor­ malities such as pes cavus and kyphoscoliosis. Cardiac lesions may include hypertrophic cardiomyopathy. Optic atrophy is usually present. There is a higher incidence of diabetes mellitus.

Occult Neuroblastoma

A child with acute cerebellar ataxia, hyperkinetic spon­ taneous movement of eyes in many directions (opso­ clonus) and myoclonic jerks of face and body should always be investigated for occult malignancy, especially neuroblastoma.

Refsum Disease

It is due to disturbances in phytanic acid metabolism. Clinical features include ataxia, atypical retinitis pigmen­ tosa with night blindness, deafness, ichthyosis and con­ duction defects in the heart. Protein level in CSF is high. These patients should be treated by excluding green vegetables (rich in phytanic acid) from the diet.

involvement and a waxing and waning course may be observed. Lipidoses can also present with cerebellar features.

Developmental Disorders

Cerebellar ataxia may also occur due to rudimentary development of cerebellarfolia. It may be associated with diplegia, both spastic and flaccid, congenital chorea and mental defect. These are nonprogressive and may appear to improve with physiotherapy.

Suggested Reading

Bernard G, Shevell MI. Channelopathies: a review. Pediatr Neurol 2008;38:73-85

Nandhagopal R, Krishnarnoorthy SG. Unsteady gait. Postgrad Med 2006;82:e7-8

INFANTILE TREMOR SYNDROME------------

Infantile tremor syndrome, as reported from Indian subcontinent, is a self limiting clinical disorder in infants and young children. It has an acute or gradual onset with mentaland pychomotorchanges,pigmentary disturbances of hair and skin, pallor and tremors. The disease is now encountered less frequently.

Etiopathogenesis

The clinical features suggest a disorder of the extra­ pyramidal system. Etiologic possibilities are malnutrition, vitamin B12 deficiency and viral infections but none have been conclusively proven.

Malnutrition. Due to its close resemblance with Kahn's nutritional recovery syndrome, malnutrition was postulated as a possible etiology. However, the majority of children are not malnourished, look chubby and their serum proteins are within normal range.

Vitamin B12 deficiency. Low vitamin B12 levels, megalo­ blastic bone marrow and a prompt response to vitamin B12 therapy is described but not substantiated.

Magnesium deficiency. Low magnesium levels in the serum and cerebrospinal fluid are reported in some cases.

Infections. Seasonal incidence and cortical biopsy suggest that it might be a form of meningoencephalitis. The failure to isolate any viral antigen, consistently normal CSF, presence of pigmentary changes andpallor do not support this hypothesis.

Toxin. Epidemiologicalevidencedoes not support the view that infantile tremor syndrome is due to a toxin.

Demyelinating and Storage Diseases

Ataxia is an important component of disorders of demyelination. Visual involvement, pyramidal tract

Enzyme defect. A transient tyrosine metabolism defect mightlead to interference in melanin pigment production. Depigmentation of substantia nigra may explain the tremor. This needs further confirmation.

Clinical Features

Infantile tremor syndrome occurs in apparently plump, normal or underweight and exclusively breastfed children of age5 months to3yr. Boysare twiceas commonly affected as girls. Most cases occur in summer months in children belonging to the low socioeconomic group.

The prodromal phase lasts for 2 weeks to 2 months. In a typical case, the onset is heralded by mental or motor regression characterized by apathy, vacant look, inability to recognize the mother, lack of interest in surroundings, lethargy and poor response to bright and colored objects. There is hyperpigmentation, especially over the dorsum of hands, feet, knees, ankles, wrists and terminal phalanges. Hair become light brown, sparse, thin, silky and lusterless. There is mild to moderate pallor. At times there may be fever, upper respiratory tract infections, diarrhea, edema, hepatomegaly and a tremulous cry.

The next phase is characterized by abrupt onset of tremors, which are usually generalized. Tremors are coarse, fast, 6-12 cycles per second, of low amplitude, initiallyintermittentbut becomecontinuouslater on. Rate of tremors may vary from one limb to the other. Head is tossed from side-to-side and trunk may show twisting or wriggling dystonic movements. Tremors disappear during sleep and are aggravated during crying, playing or feeding. Tone is variable. Consciousness is retained. Averageduration ofthisphase is 2-5 weeks. Thecondition remainsstatic forsometimebeforedisappearing altogether.

During the recovery phase, pallor and pigmentation become less, the child becomes more alert. Improvement in psychomotor function is relatively slow. This phase usually lasts for one to six months but the course may be unduly prolonged with associated infections. Mortality is never directly related to the disease but may be attributedtoconcurrentinfections. Subnormal intelligence is the only longterm sequelae.

Investigations

Laboratory investigations are not pathognomonic. There is mild to moderate anemia with hemoglobin between 6-11 g/dl. Morphologyof red cells isvariable(normocytic, microcytic, macrocytic or dimorphic). Bone marrow shows normoblastic, dimorphic or megaloblastic changes. Cerebrospinal fluid is normal. Histological evaluation of liver, skin, muscle, rectum and nerve are noncontributory. Cortical biopsies reveal mild inflammatory changes. CT scan shows no abnormalities or mild atrophy. EEG may show epileptiform activity. Virological studiesarenegative.

Differential Diagnosis

Kahn nutritional recovery syndrome, infection of the central nervous system, chronic liver diseases, hypo­ glycemia, hypomagnesemia, heredofamilial degenerative diseases, phenothiazine toxicity, hyperthyroidism and megaloblasticanemiamay beconsidered in thedifferential diagnosis.

Central Nervous System -

Treatment

Treatment is largely empirical, and supportive. Iron, calcium, magnesium, vitamin B6 supplements and injectable vitamin B12 therapy is reported to help some patients. Tremors may diminish considerably after administration of propranolol. Phenobarbitone, phenytoin and antiparkinsonism drugs do not shorten the duration of tremors. Nutrition should be maintained with dietary supplementation. Parentsshould bereassured. Associated infections and secondary complications must be treated.

Suggested Reading

Kumar A. Movement disorders in the tropics. Parkinsonism Relate Discord 2002;9:69-75

Vora RM, Tullu MS, Bartakke SP, Kamat JR. Infantile tremor syndrome and zinc deficiency. Indian J Med Sci. 2002;56:69-72

CEREBRAL PALSY

Cerebral palsy (CP) is defined as a nonprogressive neuromotor disorder of cerebral origin. It includes heterogeneous clinical states of variable etiology and severity ranging from minor incapacitation to total handicap. Most of the cases have multiple neurological deficits and variable mental handicap. The term does not include progressive, degenerative or metabolic disorders of the nervous system.

It is difficult to estimate the precise magnitude of the problem since mild cases are likely to be missed. Approximately 1-2 per 100 live births is a reasonable estimate of the incidence.

Etiopathogenesis

Factors may operate prenatally, during delivery or in the postnatal period. Cerebral malformations, perinatal hypoxia, birth trauma, chorioamnionitis, prothrombotic factors, acid base imbalance, indirect hyperbilirubinemia, metabolic disturbances and intrauterine or acquired infections may operate. Most infants have multiple risk factors. Prematurity is an important risk factor for spastic diplegia while term weight babies get quadriparesis or hemiparesis. The mechanism of CP in a large proportion of cases remains unclear and primary neurological aberrations may be unfolded in future. The importance of role of birth asphyxia has been questioned by recent data and asphyxia may be manifestation of the brain damage rather than the primary etiology.

A variety of pathological lesions such as cerebral atrophy, porencephaly, periventricular, leukomalacia, basal ganglia thalamic and cerebellar lesions may be observed.

Types of Cerebral Palsy

Cerebral palsy is classified on basis of topographic distribution, neurologic findings and etiology.

Spastic Cerebral Palsy

This is the commonest form (65%) and is topographically classified into spastic quadriparesis, diplegia or hemi­ paresis. Early diagnostic features of neural damage include abnormally persistent neonatal reflexes, feeding difficulties, persistent cortical thumb after 3 months age and a firm grasp. On vertical suspension, the infant goes into scissoring due to adductor spasm with an extensor posture and does not flex his knees or thigh. The stretch tendon reflexes are always brisk. They have variable degrees of mental and visual handicaps, seizures and behavioral problems.

Spastic quadriparesis is more common in term babies and exhibits signs including opisthotonic posture, pseudo­ bulbar palsy, feeding difficulties, restricted voluntary movements and motor deficits.

Spastic diplegia is commoner in preterm babies and is associated with periventricular leukomalacia. The lower limbs are more severely affected with extension and adductionposturing, brisk tendon jerks and contractures.

Spastic hemiplegia is usually recognized after 4-6 months age. Early hand preference, abnormal persistent fisting, abnormal posture or gait disturbance may be the presen­ ting complaint. Vascular insults, porencephaly or cerebral anomalies may be associated.

A thorough screen for associated handicaps and developmental assessment is warranted.

Hypotonic (Atonic) Cerebral Palsy

Despite pyramidal involvement, these patients are atonic or hypotonic. Tendon reflexes are normal or brisk and Babinski response is positive. They are often severely mentally retarded. In cerebellar involvement, hypotonia is not associated with exaggerated reflexes. Muscles may show fiber disproportion and delayed CNS maturation is common.

Extrapyramldal CP

This form accounts for 30% of cases. The clinical manifes­ tationsincludeathetosis,choreiformmovements,dystonia, tremors and rigidity. Arms, leg, neck and trunk may be involved. Mental retardation and hearing deficits may be present. High tone audiometry should be performed. Cerebral damage following bilirubin ence-phalopathy is one of the causes.

Cerebellar Involvement

This form is seen in less than 5% of the patients. There is hypotonia and hyporeflexia. Ataxia andintentiontremors appear by the age of 2 yr. Nystagmus is unusual; mental status may be near normal in some of these patients.

Mixed Type

A proportion of the patients have features of diffuse neurological involvement of the mixed type.

Severity of Lesion

Mild cases ofcerebral palsy are ambulatory; these account for only 20% of patients. Moderately involved patients achieve ambulation by help, may be treated at outpatient level and include 50% of the patients. Severely affected children and those with multiple deficits account for the remainder.

Evaluation

Eyes. Nearly half of thepatientshavestrabismus,paralysis of gaze, cataracts, coloboma, retrolental fibroplasia, perceptual and refractive errors.

Ears. Partial or complete loss of hearing is usual in kernicterus. Brain damage due torubellamay be followed by receptive auditory aphasia.

Speech. Aphasia, dysarthria and dyslalia are common among dyskinetic individuals.

Sensory defects. Astereognosis and spatial disorientation are seen in one-third of the patients.

Seizures. Spasticpatients usually have generalized or focal tonic seizures. Seizures are more common in disorders acquired postnatally. These patients respond poorly to antiepileptic agents. Electroencephalograms show gross abnormalities.

Intelligence. About a quarter of the children may have borderlineintelligence(IQ 80-100); and about half of them are severely mentally retarded.

Miscellaneous. Inadequate thermoregulation and problems of social and emotional adjustment are present in many cases. These children may have associated dental defects and are more susceptible to infections.

Diagnosis

The diagnosis of cerebral palsy should be suspected in a child with low birthweight and perinatal insult; clinically has an increased tone, feeding difficulties and global development delay. Abnormalities of tone posture, involuntary movements and neurological deficits should be recorded. Evaluation includes perinatal history, detailed neurological and developmentalexamination and assessment of language and learning disabilities. Inborn errors of metabolism may need to be excluded by screening of the plasma aminoacids and urine organic acid, reducing substance. CT and MRI help delineate the extent of cerebral damage in a case of cerebral palsy.

Dlfferentlal Diagnosis

Neurodegenerative disorders. Progressively increasing symptoms, familial pattern of disease, consanguinity, specific constellation of symptoms and signs are usual clues for neurometabolic disorders. Failure to thrive, vomiting, seizures are significant symptoms. Laboratory investigations are necessary.

Hydrocephalus and subdural effusion. Head size is large, fontanel may bulge and sutures may separate.

Brain tumors orspaceoccupying lesions. Lesion is progressive andfeatures of increased intracranial pressure are evident.

Muscle disorders. Congenital myopathies and muscular dystrophies can mimic cerebral palsy. Distribution of muscle weakness and other features is characteristic, hypotonia is associated with diminished reflexes. The enzyme creatine phosphokinase may be elevated. EMC and muscle biopsy are diagnostic.

Ataxia-telangiectasia. Ataxia may appear before the ocular telangiectasia are evident.

Prevention

Prevention of maternal infection, fetal or perinatal insults, good maternal and neonatal care reduces prevalence. Early diagnosis, prompt adequate management plans can reduce the residual neurological and psychosocial emotional handicaps for the child andhis family.

Management

The management plan should be holistic, involve the family and be directed to severity, type of neurological deficits and associated problems. Stress on improving posture, reducingtone,preventing contracturesandearly stimulation is necessary. Identification of associated deficits is important for appropriate physiotherapy and occupationaltherapy. Symptomatictreatmentisprescribed for seizures. Tranquilizers are administered for behavior disturbancesandmusclerelaxantsmaybeusedforimprov­ ingmusclefunction. Baclofenandtizanidine helptoreduce spasticity. Diazepam may ameliorate spasticity and athetosis. Dantrolenesodiumhelpsinrelaxationofskeletal muscles. Dynamic contractures can be managed with botulinum toxin injection or alternatively nerveblockwith phenol. Plastic orthoses may help to prevent contractures, surgicalproceduresforspasticityandcontracturesmaybe required in selected patients.

Occupational therapy. The beginning is made with simple movements of self-help in feeding and dressing with progressive development of more intricate activities like typing.

Educational. The defects of vision, perception, speech and learning are managed by adequate special education experiences.

Orthopedic support. Tendon, muscle and bony surgeries may be required. Light weight splints may be required for tight tendo-Achilles and cortical thumb.

Social. The family should be given social and emotional support to help it to live with the child's handicap.

Rehabilitation and vocational guidance. Parents should help the child to adjust in the society and if possible to become

Central Nervous System -

independent by proper vocational guidance and rehabili­ tation. Severe handicapped children may need to be institutionalized.

Suggested Reading

Anttila H, Autti-Ramii I, Suoranta L et al. Effectiveness of physical therapy interventions for children with cerebral palsy: a systematic review.BMC Pediatr 2008;8:14

Game E, Dolk H, Krageloh-Mann I, et al. SCPE Collaborative Group. Cerebral palsy and congenital malformations.Eur J Paediatr Neural 2008;12:82-8

Jones MW, Morgan E, Shelton JE. Primary care of the child with cerebral palsy: a review of systems (part ll).J Pediatr Health Care 2007;21:226-37

Rosenbaum P. Cerebral palsy: what parents and doctors wa11t to know. BMJ 2003;326:970-4

DEGENERATIVE BRAIN DISORDERS

A wide variety ofhereditaryandacquired disorders cause progressive degeneration of the central nervous system. In these disorders, new developmental skills are not achieved. As the disease advances, skills already acquired may also be lost. The degenerationmay primarily involve the gray or white matter, resulting in corresponding clinical profile.

Latecasesmayhavecommonfeatures. Afluctuant course with recurrent seizures, mental deterioration, failure to thrive, infections, abnormal urine odor, skin and hair changes may point to inborn errors of metabolism. Some comm.on causes of neurodegeneration are describedbelow.

Infantile Gaucher Disease (Type II)

It is a metabolic disorder with autosomal recessive inheritance. Thelysosomal enzyme glucocerebroside beta­ glucosidase is deficient. Glucocerebroside accumulates in various tissues. Foamy reticulum cells are present in the bone marrow. Acid phosphatase is raised in the blood and tissues. The deficient enzyme can be identified in leukocytes/fibroblasts. Mortality occurs within first 3 yr of age. Clinically, these children show a characteristic triad of retroflexed head, trismus and squint. They may show hypertonia, marked feeding problems, vomiting and dysphagia. Splenomegalyandhepatomegalyare observed later. Enzyme replacement has been tried for juvenile and adult forms of this disease.

Tay-Sachs Disease (GM2 Gangllosldosls)

Inheritance is autosomal recessive. A history of consan­ guinity is usually obtained. It was earlier reported in Ashkenazi Jews but has been reported in other racial groups also. Low serum beta-hexosaminidase level is the characteristic metabolic defect. As a result GM2 ganglio­ side accumulates in the neurons. Initially, milestones are delayed. Later, there is regression of development and deathoccursby 2 to 4 yr. The baby has anabnormalstartle response to noise. Convulsions, rigidity of the extensor

group of muscles and blindness supervene after the first year.

A cherry-red spot is seen over the macular region of the retina. The head size increases. Liver and spleen are not enlarged.Sandhoff disease is described in non-Jewish people. It resembles Tay-Sachs disease clinically except forlater onset, mild visceromegaly andprogressiveataxia. Both hexosominidase A and B are deficient. These cases may show congestive heart failure and enlarged liver.

Metachromatic Leukodystrophy

Inheritance is autosomal recessive and the gene is located on chromosome 22. The characteristic metabolic defect is decreased urinary or leukocyte aryl sulphatase A activity. Clinically, the illness manifests as ataxia, stiffness starting in the second year of life. A little later, signs of bulbar involvement and intellectual deterioration are observed. Initiallythere ishypotonia,butlaterspasticitysupervenes. Characteristically, distal tendon reflexes are lost due to associatedperipheralneuropathy.Progressive intellectual impairment,opticatrophyandlossofspeechdevelopinthe courseofillness. Convulsions mayoccurin somecases. CT scan and MRI reveal abnormal white matter finger like projections,suralnervebiopsy may reveal metachromatic granules and the enzyme arylsulfatase A is low.

Mucopolysaccharidoses

Group of disorders with autosomal recessive inheritance, Hurler syndrome is most common and is characterized by deficiency of L-iduronidase. Heparan and dermatan sulphate excretion in the urine is increased. Delayed milestones become apparent by the age of 1 yr. The facies is coarse. The child appears a dwarf with gibbus at the level of Ll vertebra. Liver and spleen are enlarged. Hands are short and stubby. Deafness, haziness of cornea and valvar heart disease may be there.

Subacute Sclerosing Panencephalitis

This condition is believed to follow several months to years after an attack of measles. The usual age of onset is between 5 and 15yr.In the early stages, minor personality changes may be observed and school performance deteriorates. Later, slow myoclonic jerks in the limbs and trunk are observed. Progressive neurologic deterioration occurs. Electroencephalogram showsstereotypedperiodic slow waves with high voltage and a burst suppression pattern. Diagnosis is established by raised measles antibodytiterinserum ( 1:256) and/or cerebrospinalfluid ( 1:4).

MENTAL RETARDATION

Mental retardation is defined as subaverage general intelligence, manifesting during early developmental period. The child has diminished learning capacity and does not adjust well socially.

Grades of Mental Handicap

Intellect comprises perception, memory, recognition, conceptualization, convergent and divergent reasoning verbal facility and motor competence. Intelligence tests devised to measure different parameters of intelligence in the different age groups include the following:

Gesell'sdevelopmentalschedules, BayleyInfant Scales, Griffith's Mental Development Scale, Wechsler Preschool and Primary Scale of Intelligence (WPPSI), Wechsler Intelligence Scale for Children (WISC), Stanford-Binet Tests (Terman-Merrillrevision),Raven'sMatrices,Denver II Development Screening Test, Good enough Draw-a­ man Test, Adaptive Behavior Scale, DEPI and II.

Indian adaptations of some of these are: Kulshrestha or Karnath adaptations of the Stanford-Binet test, Phatak adaptation of the BayleyScales,Malin's adaptation of the WISC,VinelandSocialMaturityScale andBhatia'sBattery of Performance Tests.

The intelligence quotient (IQ) is calculated according to the formula: mental age divided by chronological age, multiplied by 100.

The degree of mental handicap is designated mild, moderate, severe and profound, for IQ levels of 51-70, 36-50, 21-35 and 0-20, respectively. An IQ level of 71 to 90 is designated borderline intelligence and is not included in mental handicap.The terms educable and trainable are used formildandmoderatementalhandicap,respectively,while the severe and profoundly handicapped are designated custodian. However,all levels ofmentallyretardedchildren are educable and trainable to some extent.

Prevalence

In the general population, 2 to 3% of children have an IQ below 70. Nearly three-fourths of such cases are mildly handicapped. About 4 per 1,000 (or 0.4%) of the general population are more severely handicapped with an IQ below 50.

Etiology

It is difficult to incriminate a single factor in etiology of mild mental retardation. Majority of cases are idiopathic. Inmoderatetoseverementalretardation the cause iseasier to identify (Table 18.10).

Predisposing Factors

Low socioeconomic strata. These children are exposed to several environmental causes of mental handicap, such as inadequate nutrition of mother and child, poor antenatalandobstetric care,lackofimmunization,delayed and inappropriate treatment of infections, and unsatis­ factory environmental stimulation.

Low birthweight. The small for gestational age infant has a poorer longterm prognosis for postnatal development than preterm infants of equalweight,who are appropriate for gestational age. However, even the preterm infant is