6 Bone Disorders
OPHTHALMOLOGICAL FEATURES
Raised intraocular tension is found in one third of SWS with buphthaloms.
Episcleral hemangioma was found in all patient with SWS with glaucoma.
Homonymous hemianopic field defect are known.
Rarely retinitis pigmentosa is also reported with SWS.
IMAGING
X-ray of skull reveals pathognomic feature of intracranial calcification with double contour, like a railway line.
Fig. 7.4: Sturge-Weber syndrome facial nevus (portwine stain)
Fig. 7.5: Ataxia telangiectasia.Note right temporal bulbar telangiectasia
CT scan will reveal occipitoparietal calcification. Calcification is usually on the outer part of cortex. It is unilateral on the side of the nevus. Rare cases have been reported with bilateral calcification some time with bilateral nevus. Atrophy of affected hemisphere often developed.
Microcephaly has been reported in some cases.
MRI ranks superior to CT because it detect white matter changes and extent of the lobar involvement with degree of cortical atrophy. PET scans are used for better functional imaging.
Carotid arteriography reveals slowing of circulation in angiomatous vessel.
MANAGEMENT
Multiple antiepileptic drugs are usually required to control seizure.
Surgical: The hemispherectomy has been tried in selected cases with refractory seizures.
Hoffman’s reviewed the result of hemispherectomy in seven children, 6 of them under 11 month of age followed up for 1-13 yrs. 4 had excellent results, two were rendered hemiparetic and one died of recurrent hemorrhage.
Flash lamp pulsed laser therapy gives good cosmetic result in portwine stain. Pulsed dye laser now seems good in children for the management for raised intraocular tension and buphthalmos.
ATAXIA TELANGIECTASIA (Fig. 7.5)
Ataxia telangiectasia is rare autosomal recessive disorder with clinical feature of progressive cerebellar ataxia, oculocutaneous telangiectasia, chronic sino-pulmonary disease and high incidence of malignancy. The basic defect is in DNA metabolism and repair. The condition is associated with variable immunodeficiency state.
NEUROLOGICAL FEATURES
Ataxia becomes evident in early childhood and progress till the age of 10 to 12 years. Occulomotor apraxia, hypotonia, diminished reflexes, generalized muscular weakness become obvious late.
OPHTHALMOLOGICAL FEATURES
Conjuctival telangiectasis appeared between 3rd and 4th year of age, sometime confused with angular conjunctivits.
CUTANEOUS FEATURES
Cutaneous telangiectasia observed later in course of illness. Premature aging of skin and hair, recurrent skin infection are other reported features.
Recurrent pulmonary infection and malignancy are two common causes of death. Low level of IgA and IgE with high levels of IgM, serum alpha—fetoprotien and Carcino-embryonic antigen are supportive to the diagnosis of ataxia telangiectasia.
PARRY-ROMBERG SYNDROME (Fig. 7.6) Parry-Romberg syndrome is a rare disorder characterized
by slowly progressive hemifacial atrophy, distinctive changes of the eyes and hair. Symptoms and physical findings usually become apparent during the first or second decade of life. In rare cases, the disorder is apparent at birth. In most cases, Parry-Romberg syndrome appears to occur sporadically.
Neurological Features
Episodes of uncontrolled seizures, trigeminal neuralgia and migraine like headaches.
Cutaneous Manifestations
Initial facial changes usually involve the tissues above maxilla or nasolabial fold and progress to involve the angle of the mouth, the areas around the eye, the brow, the ear, and sometimes neck. In most cases, progressive tissue wasting is limited to one half of the face, usually the left side. Affected areas may demonstrate atrophy of subcutaneous tissue and underlying cartilage, muscle or bone.
In addition, the skin may become hyperpigmented vitiligo is rarely reported. Atrophy of half of the upper lip and tongue, or wasting of the roots of certain teeth on the affected side also seen.
In many cases, hair abnormalities may also appear on the affected side including whitening, bald patches, loss of eyelashes and eyebrow.
MANAGEMENT
In most affected individuals, hemifacial atrophy typically progresses over approximately three to five years and then ceases. Plastic surgery of the face should be deferred till progression of facial atrophy.
CUTIS VERTICIS GYRATA (Figs 7.7A and B)
This is a rare disease characterized by convoluted folds over scalp of variable thickness resembling gyral pattern. Skull shape is also deformed often microcephaly. Neurological features includes mental retardation, seizures, spasticity, deafness. Ophthalmological abnormalities includes cataract, strabismus, blindness, retinitis pigmentosa.
Fig. 7.6: Parry-Romberg syndrome.
Left facial atrophy with hyperpigmen-tation of forehead
KLIPPEL-TRNAUNAY-WEBER SYNDROME (Figs 7.8A to D)
A noninheritable condition. It is charecterized by triad of cutaneous vascular malformation, bony and soft tissue hypertrophy and venous varicosity.
The anomaly is present at birth and usually involves a lower limb but may involve more than one and portions of the trunk or face. The vascular lesion most often is a nevus flammeus, generally localized to the hypertrophied area. Venous blebs and/or vesicular lymphatic lesions may be present on their surface. Thick-walled venous varicosities typically become apparent ipsilateral to the vascular malformation after the child begins to ambulate.
Arteriograms, venograms, and CT or MRI scans may delineate the extent of the anomaly, but surgical correction or palliation is often difficult.
Supportive care includes compression bandages for varicosities, surgical treatment may help carefully selected patients. Leg length differences should be treated with orthotic devices.
Figs 7.8A to D: Klippel-Trnaunay-Weber syndrome. (A) (B) New born with the vascular nevi and asymmetrical right limb hypertrophy. (C) (D) New born with hypertrophy nevus over left lower limb
Figs 7.7A and B: Cutis Verticis Gyrata—(A) Family with cutis verticis gyrata with care taker.
(B) Vertical skin folds over scalp
A B
A
C D
B
WAARDENBURG SYNDROME (Figs 7.9A and B)
Autosomal dominant disorder due to defective migration and differentiation of neural crest cells. It is characterized by heterochromic irises, lateral displacement of medial canthi dystopia canthorum, broad nasal root, deafness, a white forelock and hypopigmented cutaneous lesion.
Figs 7.9A and B: Waardenburg syndrome (A) Unilateral hetrochromia iridae.
(B) Note hetrochromia iridae in a child and his grandmother, there was hearing loss in both
NEUROCYSTICERCOSIS (Figs 7.10A to C) INTRODUCTION
It is most common parasitic disease of CNS caused by larval form of Taenia solium. When the cysticercus cysts are present in the brain it is called neurocysticercosis.
It is caused by eating improper cooked pork and also spread by orofecal route. The most common age of presentation is school age group.
Figs 7.10A to C: (A) White flat ribbon like adult parasite Taenia solium. (B) A boy infested with Taenia solium has passed adult worm in stool. His parent brought the specimen to us with curiosity (C) CT scan head depicting single ring enhancing lesion with surrounding edema
A B
A B C
Life cycle: Adult worm is carried in human intestine (definite host). The eggs are excreted in the faces are ingested by pig (intermediate host). The ingestion of infected uncooked pork, raw vegetables contaminated with sewage and human excreta causes the larval form to enter in the human body. The larval form enters the circulation and spread into most of the tissue. Larva forms the cysts in the CNS, ranges from 4 to 20 mm. It contains transparent fluid and contains thin, whitish friable membrane. Scolex is visible as invagination of 2 to 3 mm of membrane. There are four stages of the parasite.
• Vesicular stage—This is the viable cystic stage with scolex and without inflammatory reaction around it.
• Cysticercus granuloma—The vesicular stage is converted into granuloma after 1-5 years.
It consists of cyst filled with jelly like whitish fluid and is covered by dense fibrous capsule. The scolex degenerates and forms eccentric mural nodule.
• Granulomatous nodular stage—It is small size lesion covered by thick wall with no scolex.
• Calcified stage—All cysts degenerate and calcified later on.
The first three stages represent active form and fourth one inactive form of NCC. Live cysts and granuloma are symptomatic ‘active’ while residual calcifications and gliosis are considered ‘inactive’.
Clinical features—Seizures are the most common presentation of NCC. Almost all type of seizure are noted in NCC. Raised intracranial pressure, headache, hemiplegia, meningoencephalitis, learning disability, and psychomotor problems. The youngest child described was 9 months.
Diagnosis—NCC is diagnosed 1. Clinical features. 2. Immunological tests. 3. Cerebrospinal fluid. 4. Neuroimaging. Serology, CSF studies, stool examination, radiology of leg muscle and funduscopy are usually not cost effective in children as the parasite load is not high in children.
• Immunological tests—NCC is diagnosed by immunological test of serum and CSF. ELISA for IgM antibodies has sensitivity of 50 percent and specificity of 70 percent in serum and 87 percent sensitivity and 95 percent specificity in CSF. The enzyme linked immunoelectrotransfer blot (ELTB) assay is 100 percent specific and 98 percent sensitive for diagnosis of NCC.
• CSF examination shows pleocytosis mostly lymphocytes and eosinophils.
• Neuroimaging—CT scan and MRI helps in accurate diagnosis of NCC. CT scan pickup 60 to 75 percent cases of NCC. It shows hypodense cystic lesion with eccentric hyper density indicating scolex, on contrast CT it appears as ring enhancing. Lesions are mainly at grey-white junctions in parietal, frontal and occipital lobes and are rare in temporal lobe and the posterior fossa. The tuberculoma, a common differential diagnosis, on the other hand, is seen more in basal region. MRI pickup early parenchymal cyst and edema.
Radiological criteria for diagnosis of NCC according to Rajshekhar V1 et al are as follows.
MRI features—Single, small well defined lesion less than 20 mm, contrast enhancement, ring, disc oval lesion, perifocal edema, absence of mass effect, corticomedullary junction location.
CT features—Multiple low-density lesions with or without enhancement, diffuse bilateral low-density pattern, chinked pattern, calcified lesions, scolex, meningeal obstruction, obstructive hydrocephalus, up to three lesions, solitary lesions, communicating hydrocephalus.
Treatment
• Cysticidal drugs—its use in NCC is controversial. Present consensus in that the intracranial lesion improves of its own and use of cysticidal drugs probably expedite the natural course of disease and chance of local scarring and later calcification is increased. Main indication are said to be cysticercosis meningitis and intracranial hypertension. Drugs used are Praziquental 50 mg/kg/day in three divided doses for 14 days. Albendazole 15 mg/kg/day for 28 days.
• Corticosteroids—is indicated when patient is under cysticidal drugs. It combat the symptoms caused by parasite death.
• Anticonvulsant—either carbamazepine or phenytoin is adequate in controlling the seizures.
The duration to which these drugs are used in still controversial. They are used from 6 to 18 months.
BELLS PALSY (Figs 7.11A and B)
It is the acute idiopathic paralysis of the face caused by dysfunction of facial nerve.
The pathogenesis is supposed to be viral infection possibly herpes simplex there is some component of postviral immune mediated demyelination.
The incidence is supposed to be 3/100,000 in first decade, 10/100,000 in the second and 25/
100,000 in adults.
Bells palsy is almost unilateral except in one percent cases where it is bilateral.
The facial nerve is predominantly a motor nerve and supplies all the muscles concerned with facial expression and the stapedius muscle. It has very small sensory component called – the nervus intermedius of Wrisberg. It conveys taste sensation from anterior third of the tongue and cutaneous impulse from the anterior wall of the external auditory canal.
Figs 7.11A and B: Facial palsy. (A) Left facial palsy. (B) Left facial palsy in a boy note it becomes obvious while closing the eyes, left half of the face droops
A B
Clinical features
• A history of viral infection and upper URI is seen.
• The features of neuritis like pain, tingling in the ear canal in the ipsilateral ear always precede the palsy.
• The half of the face on the affected side sags and enlarges the palpebral fissure.
• In an attempt to use the muscle of expression the face is pulled to the normal side. There is difficulty in eating and drinking, the fluid leaks from the weak corner of the mouth.
Depth of nasolabial fold is reduced on the affected side.
• The most common portion of the facial nerve involved is the portion within temporal bone, which impairs the taste, lacrimation and salivation (due to involvement of chorda tympanic branch) and induces hyperacusis (due to involvement of nerve to stapedius muscle).
• The muscle remains week for 2 to 4 weeks and then strength returns to normal gradually.
Diagnosis: The diagnosis is mostly clinical but thorough clinical and neurological examination is needed to rule out other problematic conditions. Patients ear is to be examined for herpetic vesicles (Ramsay Hunt syndrome).
Imaging is required when facial palsy is in association with other neurological disorder or if facial palsy persists for more than a month.
Bells palsy has to be differentiated from upper motor neuron lesion of facial nerve. In lower motor neuron lesion whole half of affected side is paralysed while in upper motor neuron lesion upper half of the face (forehead) is spared.
Bilateral facial palsy though very rare is seen in Guillian-Barre syndrome, Sarcoidosis and Melkersson-Rosenthal syndrome later is triad of facial palsy, recurrent facial edema and plication of tongue.
Management—to maintain the moistness of the cornea artificial tears are used. Protect the eye while playing by covering. Children with facial palsy do not require corticosteroid as compared to adults. If at all it is planned to start in older child, hypertension and infection has to be ruled out.
MARCUS-GUNN PHENOMENON (Figs 7.12A and B)
Marcus-Gunn phenomenon or facial synkinesis means that attempts to move one group of facial muscle results in contraction of associated muscles. It is usually seen during anomalous regeneration of the facial nerve. For examples
Opening of jaw may cause closure of the eyelids on the corresponding side (jaw-Winking).
If the fiber originally connected with the muscles of the face later innervate the lacrimal gland, anomalous secretion of the tears (crocodile tears) may occurs while eating.
If the fiber originally connected with orbicularis oculi innervates the orbicularis oris, closure of eyelids causes retraction of the mouth.
Figs 7.12A and B: Marcus-Gunn phenomenon. (A) Demonstration of Marcus-Gunn phenomenon. On an attempt to move the lower jaw, as in the act of sucking the bottle, the left eyelid is retracting upwards. (B) Note the retraction of left upper eyelid making the eyeball quite prominent
MYASTHENIA GRAVIS (Figs 7.13 A to D)
The immune mediated myasthenia gravis is seen from late infancy to adult life, though some congenital forms are also known.
There are two clinical forms seen: Ocular myasthenia, in which the eye muscle is primarily or exclusively affected but the facial and limb muscle may also be mildly involved, and generalized myasthenia, in which weakness of bulbar and limb muscles is moderate to severe.
Clinical features
• Ptosis and diplopia are the common presentation in myasthenia gravis. Ptosis may be unilateral or bilateral.
• Children with ocular myasthenia have mild weakness of the face and easy fatigability.
This condition has relapses and remission. At least 20 percent of patient has permanent remission.
• Children with generalized myasthenia have generalized weakness, dysarthria, dysphasia, and difficulty in chewing and limb fatigability. In this condition remission is rare, Later in the course of the disease respiratory insufficiency (myasthenic crisis) occurs. There are
Figs 7.13A to D: Myasthenia Gravis: (A) (B) Bilateral ptosis and facial weakness. (C) 8-year-old patient presented with ptosis which aggravates during the end of the day, (D) Watch the response to inj neostigmine over the ptosed eyes and facial alertness, this test is also one of the diagnostic for myasthenia gravis
A B C D
B A
other autoimmune disorders associated with generalized myasthenia. Thymoma is present in 15 percent adult cases and in 5 percent in children with generalized myasthenia.
• Myasthenic Crisis—Exacerbation of myasthenia and need for artificial ventilation occurs in some 10 percent of cases with myasthenia. These patients are to be monitored very closely.
Investigations
• Edrophonium Test (Tensilon test)—This test is used to diagnose both forms of myasthenia gravis. Edrophonium is short acting anticholinesterase given intravenously at a dose of 0.15 mg/kg. Ptosis responds better by edrophonium than ocular motor paralysis.
• Vital capacity detecting especially in generalized form.
• Chest X-ray, CT or MRI chest to rule out associated thymoma.
• Serum acetylcholine receptor antibodies.
• Plasma thyroxine to rule out associated thyroid disorders.
• Antinuclear antibody, rheumatoid factor, and antithyroid antibodies may be positive.
• EMG abnormality includes decremental response to titanic train stimulation at 5-10 Hz and evidence of neuromuscular blockade is seen on single fiber EMG in the form of jitter and blocking of motor action potential.
Osserman’s Grading of Myasthenia.2 (1)- Myasthenia gravis severity can be graded clinically by Osserman’s grading.
• Grade I : Ocular myasthenia.
• Grade II: Mild generalised myasthenia with slow progression; no crisis; drug responsive.
• Grade III: Acute fulminating myasthenia; rapid progression to severe symptoms of respiratory crisis and poor drug response; high incidence of thymoma; high mortality rate.
• Grade IV: Late severe myasthenia; same as grade III but takes two years to progress from class I to II; high mortality rate.
Management
• Anticholinesterase therapy—Neostigmine in the dose of 0.5 mg/kg every 4 hrly in children younger that 5 years of age, and .25 mg/kg in older children, not to exceed 15 mg. The dose is slowly increased to maximum tolerable. Diarrhea and gastrointestinal cramp are the limiting factors.
• Thymectomy—if performed early in the course of the disease remission can be achieved within three years.
• Immunosuppression—by steroids, azathioprim, ciclosporin, plasmapheresis and thymectomy are other forms of treatment.
• Avoid D—penicillamine therapy is avoided as it can precipitate myasthenia so are the aminoglycosides.
RETT SYNDROME (Figs 7.14A and B) DEFINITION
Rett syndrome is neurodegenerative disorder occurs only in girls and the prevalence is estimated to be 1:10,000 to 1: 20,000. A period of normal development followed by loss of developmental skill and with characteristic hand movement.
GENETICS
This is caused by mutation in the gene encoding methyl-CpG-binding protein-2. The gene maps to chromosome Xq28. The precise mechanism of inheritance by which an X-linked disorder occurs in only female is not yet established.
Figs 7.14A and B: Rett syndrome: (A) Hand wringing and mouthing movements in a girl aged 2 years (B) Note the stereotype hand washing movement and mouthing in a 1-year-old patient
CLINICAL FEATURES
Affected girls are normal during the first year. Developmental arrest usually begins at 12 months but may appear as early as 5 months but as late as 18 months.
The initial features are deceleration of head growth leading to microcephaly and rapid developmental regression. It is characterized by loss of language skills, decreased use of hands, gait ataxia, seizures and autistic behavior.
There is characteristic feature of this syndrome is loss of purposeful hand movement before age three. They are replaced by stereotype activity that looks like hand wringing of washing.
Disorganized breathing with hyperventilation. Seizures are common and is seen in 75-80 percent patient and vary from tonic clonic, partial complex seizures, Myoclonic seizures occur in most children between the ages of 1 and 3 years.
DIAGNOSIS
So far no rational interpretation has been presented to correlate these derangements with underlying disease and the diagnosis is purely clinical. Recently mutation in MECP2 seems to be the main cause of Rett syndrome in 77 percent cases.3, 4
TREATMENT
No specific therapy has been suggested. Anticonvulsant has been used to control the convulsion.
A B
ANGELMAN SYNDROME (Figs 7.15A and B) INTRODUCTION
In 1965, Dr Harry Angelman, an English physician, first described three children with features of Angelman syndrome. They all have stiff, jerky gait, excessive laughter and seizures.
SYNONYM
Happy puppet syndrome
Happy puppet syndrome