pediatric neurology

PEDIATRIC NEUROLOGY

‫بسم هللا الرحمن الرحيم‬

DR SAMED ALSALMI

Neural tube defects and hydrocephalus

Neural tube defects result from failure of normal fusion of the neural plate to form the neural tube during the first 28 days following conception. Their birth prevalence in the UK has fallen dramatically from 4 per 1000 live births in the 1970s to 0.15 per 1000 live births in 1998 and to 0.11 per 1000 live births in 2005 . This is mainly because of a natural decline, as well as antenatal screening.

The reason for the natural decline is uncertain but may be associated with improved maternal nutrition. It is well recognised that mothers of a fetus with a neural tube defect have a 10-fold increase in risk of having a second affected fetus. It has been shown that supplementing these mothers' diet with high doses of folic acidl " markedly reduces this risk. It is now recommended that women who have had a previously affected infant and are planning a pregnancy should take high-dose folic acidl " periconceptually. Low-dose periconceptual folic acidl " supplementation

Anencephaly

This is failure of development of most of the cranium and brain. Affected infants are stillborn or die shortly after birth. It is detected on antenatal ultrasound screening and termination of pregnancy is usually performed.

Encephalocele

There is extrusion of brain and meninges through a midline skull defect, which can be corrected surgically. However, there are often underlying associated cerebral malformations

term infant with an anterior encephalocele. In the Western hemisphere and Europe, the majority of encephaloceles are posterior, whereas in the Far East (the majority of encephaloceles are anterior.

A posterior encephalocele in an infant may be difficult to distinguish from a cervical meningocele. It is both a posterior encephalocele and cervical myelomeningocele when there is involvement of both the bony skull and spine. Cervical myelomeningoceles are usually not associated with other neurologic abnormalities

Anencephaly is a developmental defect in the brain with an open cranium resulting from failure of the anterior neural tube to close. It is a major open neural tube defect in which there is absence of skull bones, cranial vault, and incomplete development of the brain. Malformation of other organs may occur such as adrenal hypoplasia and genitourinary abnormalities.. Most of these infants are stillborn and the remainder die in the immediate neonatal period.

Spina bifida occulta

This failure of fusion of the vertebral arch is often an incidental finding on X-ray, but there may be an associated overlying skin lesion such as a tuft of hair, lipoma, birth mark or small dermal sinus, usually in the lumbar region. There may be underlying tethering of the cord (diaste-matomyelia) which, with growth, may cause neurological deficits of bladder function and lower limbs. The extent of the underlying lesion can be delineated using ultrasound and/or MRI scans. Neurosurgical relief of tethering is usually indicated

This infant had a midline small skin tag with depigmentation of the skin in the lumbosacral region. The MRI revealed a tethered cord.

Midline pilonidal dimples or sinuses are common dimple, an MRI should be performed to exclude a neural tube defect. The MRI was normal in this infant

midline hair tuft in the lumbosacral area. This infant had a tethered cord on MRI study. Hair tufts, skin tags, sinuses, and abnormal pigm that occur in the midline neurologic abnormality.

midline tuft of hair with a pigmented nevus in the lumbosacral area. This should alert one to the possibility of an associated underlying neurologic abnormality

Meningocele and myelomeningocele Meningoceles usually have a good prognosis following surgical repair. Myelomeningoceles ( can cause a wide range of problems including: variable paralysis of the legs  muscle imbalance which may cause dislocation of the hip and talipes  sensory loss  bladder denervation (neuropathic bladder)  bowel denervation (neuropathic bowel)  scoliosis  hydrocephalus from the Arnold-Chiari malformation (herniation of the cerebellar tonsils through the foramen  magnum), leading to disruption of CSF flow Physiotherapy is required to prevent joint contractures and strengthen paralysed muscles. Walking aids or a wheelchair may be required to permit mobility. With sensory loss, skin care is required to avoid the development of skin damage and ulcers. An indwelling catheter may be required for bladder denervation, or intermittent urinary catheterisation may be performed by parents or by older children themselves. Urine samples should be checked regularly for infection. Continuous prophylactic antibiotics may be necessary. The child should be monitored for early evidence of hypertension and renal failure. Medication (such as ephedrinel " or oxybutinin) may improve bladder function and improve urinary dribbling. Bowel denervation requires regular toileting, and laxatives and suppositories are likely to be necessary with a low roughage diet for lesions above L3. Scoliosis is monitored and may require surgical treatment. Ventricular dilatation from Arnold-Chiari malformation is often present at birth and 80% of affected infants require a shunt for progressive hydrocephalus during the first few weeks of life. Those children destined to be the most severely disabled have a spinal lesion above L3 at birth. They are unable to walk, have a scoliosis, neuropathic bladder, hydronephrosis and frequently develop hydrocephalus. Modern medical care has improved the quality of life for severely affected children. Most affected infants are now treated with closure of the lesion of the back soon after birth. Their care is best managed by a specialist multidisciplinary team.

This infant has a lumbar meningocele which is an example of a closed neural tube can occur anywhere along this axis. Meningoceles occur when the membranes surrounding the spinal cord bulge outward through a dorsal defect in spinal canal. The resulting mass may be tense or fluctuant and is covered by intact skin.

lumbosacral meningocele

thoracic myelomeningocele

Thoracolumbosacral myelomeningocele

Lumbosacral meningocele area is the most common location for both meningoceles and myelomeningoceles. Infants with meningoceles and myelomeningoceles may have an Arnold-Chiari malformation and a high percentage develop hydrocephalus

lumbar meningocele which is an example of a closed neural tube defect. and defects of fusion can occur anywhere along this axis. The resulting mass may be tense or fluctuant and is covered by intact skin

Hydrocephalus In hydrocephalus there is obstruction to the flow of cerebrospinal fluid, leading to dilatation of the ventricular system proximal to the site of obstruction. The obstruction may be within the ventricular system or aqueduct (non-communicating or obstructive hydrocephalus), or at the arachnoid villi, the site of absorption of CSF (communicating hydrocephalus Causes of hydrocephalus Non-communicating (obstruction in the ventricular system)  Congenital malformation  Aqueduct stenosis  Atresia of the outflow foramina of the fourth  ventricle (Dandy-Walker malformation)  Arnold-Chiari malformation  Posterior fossa neoplasm or vascular malformation  Intraventricular haemorrhage in preterm infant Communicating (failure to reabsorb CSF) Subarachnoid haemorrhage Meningitis: e.g. pneumococcal, tuberculous in infants with hydrocephalus, as their skull sutures have not fused, the head circumference may be disproportionately large or show an excessive rate of growth. The skull sutures separate, the anterior fontanelle bulges and the scalp veins become distended. An advanced sign is fixed downward gaze or sun setting of the eyes . Older children will develop signs and symptoms of raised intracranial pressure. Hydrocephalus may be diagnosed on antenatal ultrasound screening or in preterm infants on routine cranial ultrasound scanning. For suspected hydrocephalus initial assessment is with cranial ultrasound (in infants) or CT and MRI scan. Head circumference should be monitored over time on centile charts. Treatment is required for symptomatic relief of raised intracranial pressure and to minimise the risk of neurological damage. The mainstay is the insertion of a ventricular shunt , but endoscopic treatment and ventriculostomy can now be performed. Shunts can malfunction due to blockage or infection (usually with coagulase-negative staphylococci). They then need replacing or revising. Overdrainage of fluid can cause low-pressure headaches but the insertion of regulatory valves can help avoid this.

Transillumination of the skull of an infant with a DandyWalker malformation. Note the bulging occiput and enlargement of the head, and a large posterior fossa cyst.

This term infant had macrocephaly, a prominent brow, and distended scalp veins. Transillumination was positive with the lack of underlying brain tissue being consistent with hydranencephaly.

Microcephaly in a term infant with congenital rubella. Microcephaly may be idiopathic or acquired as a result of intracranial pathology. It may also result from serious perinatal brain injury

CHIARI MALFORMATION TYPE I: DISPLACEMENT OF CEREBELLAR TONSILS INTO THE CERVICAL CANAL. GIVES SYMPTOMS IN ADOLESCENCE OR ADULT LIFE. (HEADACHE, NECK PAIN) NO HYDROCEPHALUS

TYPE II : PROGRESSIVE HYDROCEPHALUS AND MYELOMENINGOCELE. ELONGATION OF THE 4TH VENTRICLE. DISPLACEMENT OF INFERIOR VERMIS, PONS, AND MEDULLA INTO CERVICAL CANAL

DANDY-WALKER SYNDROME CYSTIC EXPANSION OF THE 4TH VENTRICLE IN THE POSTERIOR FOSSA. DEVELOPMENTAL FAILURE OF ROOF OF 4TH VENTRICLE DURING EMBRYOGENESIS. 90 % HAVE HYDROCEPHALUS PROMINENT OCCIPUT

Transillumination of the skull of the same infant with congenital hydrocephalus

This term infant shows massive head enlargement as the result of congenital hydrocephalus. This results from overproduction or obstruction of the circulation of the cerebrospinal fluid.

hydrocephalus

headache

Causes of recurrent headache Tension-type headache Migraine without aura  with aura  complicated 

Raised intracranial pressure and space-occupying lesions

Other causes: sinusitis - may cause facial pain, elicited by percussion  temporomandibular joint discomfort - from dental malocclusion, worse on chewing  medication - side-effect  refractive errors - rare cause, but check vision  head trauma  solvent, drug and alcohol abuse 

Causes of acute headache Febrile illness  Migraine  Stress  Acute sinusitis  Meningitis/encephalitis  Head injury  Subarachnoid or intracerebral haemorrhage  Benign intracranial hypertension  Medications, alcohol, solvent or drug abuse  Other triggers: ice-cream, from reflex neuralgia 

International Headache Society Classification Migraine without Aura 1. At least five attacks fulfilling 2 to 4 2. Attacks last 2 to 72 hours 3. At least two of the following: Unilateral Pulsating Moderate to severe intensity Aggravated by routine physical activity 4. During headache at least one of the following: Nausea or vomiting Photophobia and phonophobia Migraine with Aura 1. At least two attacks fulfilling 2 2. At least three or more of the following: One or more reversible symptoms indicating focal cerebral cortical or brainstem dysfunction At least one aura symptom develops gradually over 4 or more minutes, or two or more symptoms occur in Succession No aura lasts more than 60 minutes Headache follows aura with a free interval of 15 days/month for >6 months 2.fulfilling 3 and 4 listed above for episodic tension Headache Associated with Trauma Headache Associated with Disorder of Sinuses or Other Facial or Cranial Structures

Differential Diagnosis of Headaches Based on the Time Course New Acute Severe Headache Viral syndrome Acute sinusitis, pharyngitis Migraine Migraine variant Meningoencephalitis Intracranial hemorrhage Head traumaBrain tumor Substance abuse (e.g., cocaine) Medications Carbon monoxide poisoning Ventriculoperitoneal shunt malfunction Hypertensive encephalopathy Intracranial venous sinus thrombosis Recurrent Acute Headaches Migraine and migraine variants Tension-type headache Substance abuse Medications Postepileptic event Cluster headaches Intermittent raised intracranial pressure Chronic Progressive Headaches Hydrocephalus Brain tumor Intracranial infections (e.g., brain abscess, infection of the ventriculoperitoneal shunt, tuberculosis, cryptococcal Meningitis Chronic subdural hematoma Pseudotumor cerebri (benign intracranial hypertension) Primary or secondary central nervous system vasculitis

Differential Diagnosis of Headache 7. Traction headache 1. Vascular headache of migraine type

a. Primary or metastatic tumors: meninges, brain, or

a. Classic migraine b. Common migraine

c. Cluster headache

vasculature Click to edit the outline  b. Hematomas: epidural, subdural, parenchymal text format c. Abscesses: epidural, subdural, parenchymal

d. Hemiplegic and ophthalmoplegic migraine e. “Lower half ” headache 2. Muscle-contraction (tension) headache

Second Outline  d. Post–lumbar puncture headache Level cerebri e. Pseudotumor Third Outline  a. Intracranial: meningitis, subarachnoid Level hemorrhage, iatrogenic Fourth Outline  (postoperative, postpneumoencephalogram, Level etc.), arteritis, phlebitis Fifth Outline  b. Extracranial: vasculitis, cellulitis Level 9. Ocular headache Sixth pressure,  Increased intraocular ocular muscle Outline contraction, trauma, tumor, inflammatio 8. Headache due to overt cranial inflammation

3. Combined headache: vascular and muscle-contraction 4. Headache of nasal vasomotor reaction 5. Headache of delusional, conversion or hypochondriacal states 6. Nonmigrainous vascular headaches a. Systemic infectionsb. s: hypoxic states, carbon monoxide caffeine withdrawal, cerebral ischemia, postconcussion or postconvulsive states, “,” hypoglycemia, hypercapnia, hypertensive states, pheochromocytoma n

10. Aural headache Trauma, inflammation, infection, tumor of the ear 11. Nasal/sinus headache Allergic, infectious, inflammatory, traumatic, tumor of the nose and/or paranasal sinuses 12. Dental headache Infection, trauma, tumor, inflammation, iatrogenic Temporomandibular joint syndrome 13. Cranial/neck headache Disorders of cervical spine, cervical nerve roots, scalp/neck muscles, tendons, ligaments 14. Cranial neuritides Traction, trauma, inflammation, infection, tumor 15. Cranial neuralgia Trigeminal Glossopharyngeal

Headache History

General Medical History Presence of other acute medical problems or symptoms Chronic medical problems Current orPrevious medication used for headaches Previous long-term medication use or overuse Intake of caffeine, vitamin A, alcohol, cocaine Pattern When did the headaches begin? Frequency and change in frequency Duration of headaches Pattern to the time of day Presence of headaches on weekends, weekdays Are headaches preceded by a warning? Description of Pain Location Quality Intensity Effects of position, Valsalva maneuver, and movement Associated Factors Trauma Are headaches associated with other activity? Does any medication make the headache better? Do the following occur before, during, or immediately after the headache: visual disturbance, vertigo, weakness, paresthesias, nausea, vomiting, changes in sensorium? Family History Migraines Aneurysm (autosomal dominant polycystic kidney disease, inherited disorders of collagen synthesis)

Important Components of the Physical Examination in the Child with Headaches General Examination Airway, breathing, circulation, and blood pressure Growth, including head circumference Mental status, behavior profile Head, neck, eye, ear, nose, and throat examination for swelling, tenderness, trauma, or infection Dental examination Skin examination for rashes, neurocutaneous lesions, pallor Evidence of external trauma External bleeding, petechia Neurologic Examination Meningeal signs Fundus, eye movements, and pupillary reaction Facial asymmetry Motor strength in all extremities Deep tendon reflexes Gait Romberg sign Cerebellar signs (e.g., finger-to-nose test, rapid alternating movements, and action tremors) Palpation of shunt track if ventriculoperitoneal shunt present

Role of Neuroimaging Studies When to Order a Neuroimaging Study Abnormal neurologic findings Chronic or progressive headaches Unilateral headaches that never alternate sides Headache associated, even briefly, with alteration of sensorium Presence of papilledema Meningeal signs without fever Recent worsening Advantages of Magnetic Resonance Imaging (MRI) Most vascular malformations are detected Accurate detection of tumors in temporal lobes and posterior fossa, and small tumors that obstruct CSF flow (quadrigeminal plate and third ventricular) Paranasal sinuses usually included in the examination without special request More sensitive for detecting transependymal CSF in cases of borderline hydrocephalus Diagnostic for Chiari malformations Magnetic resonance angiography can detect many aneurysms Magnetic resonance venography can detect cortical vein and dural sinus thrombosis Advantages of Computed Tomography Less expensive and easier access than MRI May be used in patients with pacemakers, metal implants (surgical clips), and cosmetic tattoos (MRI may turn off pacemakers and dislodge the clips; tattoos distort the mage

Management The mainstay of management is a thorough history and examination with detailed explanation and advice. Imaging is unnecessary in the absence of the symptoms or signs of raised intracranial pressure or abnormal neurological signs. A headache diary can be helpful in pinpointing triggers (usually there are none) and for monitoring management. Children and parents should be informed that recurrent headaches are common. There are likely to be good and bad patches over months or years but they cause no long-term harm. Written information for the child and parents to take home is helpful. Children should be advised on how to live with and control the headaches, rather than allowing the headaches to dominate their lives. Therapeutic options include: psychological support to ameliorate particular causes of stress, e.g. bullying,  anxiety over exams or illness in friends or family relaxation and other self-regulating techniques  analgesia - paracetamol and non-steroidal anti-inflammatory drugs (NSAIDs),  which should be taken as early as possible if the severity of the headache is increasing anti-emetics - ··prochlorperazine·· and metoclopramide  serotonin (5-HT1) agonist, sumatriptan. A nasal preparation of this is licensed for  use in children over 12 years of age. Other triptans are not yet licensed in children. If headaches are frequent, usually greater than one per week, prophylactic agents can be tried. These include: pizotifen (5-HT antagonist) - but can cause weight gain and sleepiness  beta-blockers - propranolol, but contraindicated in asthma. 

Migraine

This periodic disorder is characterised by paroxysmal headache, often unilateral, and is characteristically throbbing. It is often accompanied by unpleasant gastrointestinal disturbance such as nausea, vomiting and abdominal pain and by visual disturbance. The visual disturbances include: Negative phenomena such as: hemianopia (loss of half the  visual field) scotoma (small areas of visual loss). Positive phenomena such as: fortification spectra (seeing zigzag  lines). Rarely, there are unilateral sensory or motor symptoms. Episodes usually last for a few hours, during which time children often prefer to lie down in a quiet, dark place. Sleep often relieves the bout. e oral contraceptive pill.

Migraine is classified as:

without aura (formerly called common migraine), affecting approximately 90%  with aura (formerly called classical migraine) - the headache is preceded by an  aura (visual, sensory or motor); this type affects approximately 10% (the aura may occur without a headache) complicated - associated with neurological phenomena such as ophthalmoplegia,  hemiparesis, paraesthesiae or hemidysaesthesia (altered sensation down one side of the body). It occurs in 1-2% and, rarely, results in permanent neurological deficit. Hemiparetic migraine is linked to a calcium channel defect, often dominantly inherited. Vertebrobasilar migraine gives rise to signs of posterior circulation compromise, such as nystagmus and associated vomiting and dizziness. Symptoms of tension-type headache and migraine often overlap. They are probably part of the same pathophysiological continuum; there is increasing evidence that both symptom groups result from channelopathies with vascular phenomena being secondary events. Headaches are common in first- and second-degree relatives of children with recurrent headaches. Some cases of cyclical (recurrent) vomiting and recurrent abdominal pain in young children are thought to be due to abdominal migraine. Stress at home or school may trigger headaches and make them more difficult to cope with, although for many, winding down is a trigger. A food diary helps to identify any food triggers, often cheese, chocolate, and caffeine, although they may vary with time. In girls, headaches can be related to menses and th

Tension-type headache

This is a symmetrical headache of gradual onset, often described as tightness, a band or pressure. There are usually no other symptoms, but it may be accompanied by abdominal pain and behaviour problems. It may occur daily.

Raised intracranial pressure and space-occupying lesions Headaches often raise the fear of brain tumours and may be the reason for parents to consult a doctor. Headaches due to a space-occupying lesion are worse when lying down and morning vomiting is characteristic. The headaches may also cause nighttime waking. There is often a change in mood, personality or educational performance. Other features suggestive of a space-occupying lesion are: visual field defects - from lesions pressing on the optic pathways, e.g.  craniopharyngioma (a pituitary tumour) cranial nerve abnormalities causing diplopia, new onset squint or facial nerve palsy.  The VIth (abducens) cranial nerve has a long intracranial course and is often affected when there is raised pressure, resulting in a squint with diplopia and inability to abduct the eye beyond the midline. It is a false localising sign. Other nerves are affected depending on the site of lesion, e.g. pontine lesions may affect the VIIth (facial) cranial nerve and cause a facial nerve palsy abnormal gait  torticollis (tilting of the head)  growth failure, e.g. craniopharyngioma or hypothalamic lesion  papilloedema - a late feature  cranial bruits - may be heard in arteriovenous malformations but these lesions are  rare

Conditions Associated with Pseudotumor Cerebri Intracranial Venous Drainage Obstruction Mastoiditis and lateral (sigmoid) sinus obstruction Extracerebral mass lesions Congenital atresia or stenosis of venous sinuses Head trauma Cryofibrinogenemia Polycythemia vera Paranasal sinus and pharyngeal infections Cervical or Thoracic Venous Drainage Obstruction Intrathoracic mass lesions and postoperative obstruction of venous return

Endocrine Dysfunction Pregnancy Menarche Marked menstrual irregularities Oral contraceptives Obesity Withdrawal of corticosteroid therapy Addison disease Hypoparathyroidism thyroxine treatment for hypothyroidism Adrenal hyperplasia Adrenal adenoma Hematologic Disorders Acute iron deficiency anemia Pernicious anemia Thrombocytopenia Wiskott-Aldrich syndrome Vitamin Metabolism Chronic hypervitaminosis A Acute hypervitaminosis A Hypovitaminosis A Cystic fibrosis Vitamin D–deficiency rickets Drug Reaction Tetracyclines Perhexiline maleate Nalidixic acid Sulfamethoxazole L-Asparaginase Indomethacin Miscellaneous Lyme disease Sarcoidosis

Causes of Increased Intracranial Pressure Space-Occupying Lesions Intracerebral hemorrhage Epidural hemorrhage Subdural hemorrhage Tumor Abscess Diffuse Cerebral Edema Meningitis Encephalitis Hepatic encephalopathy Reye's syndrome Acute liver failure Electrolyte shifts Dialysis Hypertensive encephalopathy Postanoxic brain injury Lead encephalopathy Uncompensated hypercarbia Head trauma Diffuse axonal injury Hydrocephalus Subarachnoid hemorrhage Meningitis Aqueductal stenosis

Idiopathic Miscellaneous

Etiological Classification of Chorea 1. Developmental and aging choreas a. Physiological chorea of infancy b. Cerebral palsy—anoxic, kernicterus c. Minimal cerebral dysfunction d. Buccal-oral-lingual dyskinesia and edentulous orodyskinesia in elderly e. Senile chorea (probably several causes) 2. Hereditary choreas

a. Huntington's disease b. Benign hereditary chorea c. Neuroacanthocytosis d. Other CNS ―degenerations‖: olivopontocerebellar atrophy, Azorean disease, ataxia-telangiectasia, tuberous sclerosis, Hallervorden-Spatz, dentato-rubral-pallido-lysian atrophy (DRPLA), familial calcification of basal ganglia, others e. Neurometabolic disorders: Wilson's disease, Lesch-Nyhan disease, lysosomal storage disorders, amino acid disorders, Leigh's disease, porphyria 3. Drug-induced choreas: neuroleptics (tardive dyskinesia), antiparkinsonian drugs, amphetamines, tricyclics, oral contraceptives, anticonvulsants, anticholinergics, others 4. Toxin-induced choreas: alcohol intoxication and withdrawal, anoxia, carbon monoxide, Mn, Hg, thallium, toluene 5. Metabolic causes a. Hyperthyroidism b. Hypoparathyroidism (various types) c. Pregnancy (chorea gravidarum) d. Hyper- and hyponatremia, hypomagnesemia, hypocalcemia e. Hypo- and hyperglycemia (latter may cause hemichorea, hemiballismus) f. Acquired hepatocerebral degeneration g. Nutritional—for example, beriberi, pellagra, vitamin B12 deficiency in infants

6. Infectious causes

Ataxia

Ataxia, from the Greek word for 'without order', describes incoordination of movement, speech and posture. This can be due to cerebellar or posterior sensory pathway problems. Cerebellar causes are more common in children. In cerebellar ataxia there is an unsteady wide-based gait, difficulty in performing repetitive and alternating movements (dysdiadochokinesis), overshooting of target-directed movement (dysmetria) and an intention tremor which becomes more pronounced when the child puts more effort into trying to hold a posture. The gait has a wide base to provide stability to compensate for the truncal ataxia. There may be associated wobble of the head, nystagmus and speech impairment with a scanning dysarthria. Cerebellar ataxia may be caused by various insults to the cerebellum: acute, from medication and drugs, including alcohol and solvent abuse  post-viral, particularly after varicella infection  posterior fossa lesions or tumours, e.g. medulloblastoma  genetic and degenerative disorders, e.g. ataxic cerebral palsy, Friedreich's ataxia and ataxia- telangiectasia.

Classification of Ataxia Congenital Ataxias Hereditary Ataxias Autosomal Recessive Ataxias Friedreich's ataxia (FRDA) Ataxia-telangiectasia (AT) Ataxia with oculomotor apraxia type 1 Ataxia with oculomotor apraxia type 2 Autosomal recessive spastic ataxia of Charlevoix-Saguenay (ARSACS) Abetalipoproteinemia Ataxia with isolated vitamin E deficiency (AVED) Refsum's disease Cerebrotendinous xanthomatosis (CTX) Marinesco-Sjogren syndrome (MSS) Autosomal recessive ataxia with known gene locus Early onset cerebellar ataxia (EOCA) X-Linked Ataxias Fragile X tremor ataxia syndrome (FXTAS) Autosomal Dominant Ataxias Spinocerebellar ataxias (SCA) Dentatorubral-pallidoluysian atrophy (DRPLA)

Nonhereditary Degenerative Ataxias Multiple system atrophy, cerebellar type (MSA-C) Sporadic adult-onset ataxia of unknown etiology

Acquired Ataxias Alcoholic cerebellar degeneration other toxic reasons (antiepileptics, lithium, solvents

Paraneoplastic cerebellar degeneration Other immune-mediated ataxias (gluten ataxia, ataxia associated with anti-GAD antibodies) Acquired vitamin E deficiency Hypothyroidism Ataxia due to physical causes (heat stroke, hyperthermia)

Friedreich's ataxia

This is an autosomal recessive condition The gene mutation (Frataxin) is an example of a trinucleotide repeat disorder. It presents with worsening ataxia, distal wasting in the legs, absent lower limb reflexes but extensor plantar responses because of pyramidal involvement, pes cavus and dysarthria. This is similar to the hereditary motor sensory neuropathies, but in Friedreich's ataxia there is impairment of joint position and vibration sense, extensor plantars and there is often optic atrophy. The cerebellar component becomes more apparent with age. Evolving kyphoscoliosis and cardiomyo-pathy can cause cardiorespiratory compromise and death at 40-50 years.

Ataxia telangiectasia

This disorder of DNA repair is an autosomal recessive condition. The gene (ATM) has been identified. There may be mild delay in motor development in infancy and oculomotor problems with incoordination and delay in ocular pursuit of objects (oculomotor dyspraxia), with difficulty with balance and coordination becoming evident at school age. There is subsequent deterioration, with a mixture of dystonia and cerebellar signs. Many children require a wheelchair for mobility in early adolescence. Telangiectasia develop in the conjunctiva, neck and shoulders from about 4 years of age. These children: have an increased susceptibility to infection, principally from an IgA surface  antibody defect develop malignant disorders, principally acute lymphoblastic leukaemia (about  10%) have a raised serum alphafetoprotein  have an increased white cell sensitivity to irradiation, which can be used  diagnostically, but the ATM gene test is now mostly used

Ataxia–telangiectasia – telangiectasias on the conjunctivae

Paroxysmal Disorders

Paroxysmal Disorders in Infants Nonepileptiform Disorders Infantile syncope* Cyanotic breath-holding spells Pallid syncope Shivering attacks Paroxysmal torticollis Extrapyramidal drug reactions, dystonia GER with dystoni metabolic encephalopathy Benign myoclonus Hyperexplexia† Sleep disordeer

Acute Symptomatic Seizures, Occasional Seizures Febrile convulsions* Meningitis, encephalitis* Head injury , child abuse Poisoning , renal, liver disease, cardiac left-to-right shunt and embolism Epileptic Syndromes West syndrome Early myoclonic encephalopathy‡ Early infantile encephalopathic epilepsy‡ Malformations of cortical development‡ Neurocutaneous disorders Tuberous sclerosis Sturge-Weber syndrome Incontinentia pigmenti Severe myoclonic epilepsy in infancy

Paroxysmal Disorders of Childhood Nonepileptiform Disorders Breath-holding spells*† equivalents, recurrent abdominal cyclic vomiting torticollis† , dystonia Benign paroxysmal vertigo† constipation* Munchausen syndrome by proxy Psychogenic seizures

Syncope‡ * TiC choreoathetos Masturbation† Daydreaming, , Hyperventilatin Sleep

Migraine and migraine Spasmodic Gastroesophageal reflux autism, coexistent

Acute Symptomatic Seizures, Occasional Seizures Febrile convulsions* Brain tumor Meningitis, encephalitis Head injury, child abuse Poisoning Is, renal, liver disease, cardiacright-to-left shunt, and embolism Epileptic Syndromes Benign partial epilepsies* Childhood absence epilepsy Lennox-Gastaut syndrome Landau-Kleffner syndrome

Symptomatic focal epilepsy Epilepsy with myoclonic absences

Syncope (fainting) Syncope, seen commonly in older children and adolescents, can often be differentiated from an epileptic seizure by history. Attacks may be preceded by warning (presyncopal) signs such as lightheadedness, blurring of vision, pallor, nausea, or diaphoresis. These warning signs are followed by a gradual loss of consciousness and a slow slump to the ground, as opposed to the more violent fall seen with a myoclonic or atonic seizure. Late in the syncopal spell, there may be a brief tonic or clonic seizure secondary to cerebral hypoperfusion and hypoxia; these are not epileptic seizures Consciousness is regained rapidly, compared with a more prolonged epileptic postictal state. A child may be tired after syncope but s not ordinarily confused for more than a few seconds. Seizure is further differentiated from syncope in that a seizure is not associated with cold, clammy skin.

Syncope is caused by transiently diminished cerebral blood flow, due to an irregular heart rate (an arrhythmia causing decreased cardiac output) decreased venous return orthostasis or Valsalva, a vasovagal mechanism (fright pain, emotional upset)( anoxic pallid ), or, rarely, cough- or micturitioni nduced reflex syncope. Vasovagal attacks often occur in a hot, crowded environment. Orthostasis is most commonly precipitated by rising from a sitting or recumbent position. A child who has an arrhythmia or who faints from any position other than standing requires a cardiac evaluation, including an electrocardiogram, echocardiogram, Holter monitor, and perhaps a tilt-table test. Orthostatic blood pressures should be documented; upon standing, a drop in pulse of more than 20 points or systolic blood pressure of more than 15 points is abnormal. The hallmark of treatment is prevention. The child should avoid precipitating factors as much as possible. During a syncopal event, the observer should allow the child to lie horizontally or with the head at a lower level than the body; lifting or raising the head can delay return of consciousness by prolonging the duration of cerebral hypoperfusion

Breath-holding spells Despite their name, breath-holding spells (BHSs) are involuntary reflex responses with a benign prognosis. They are age-related and are typically outgrown by school age. Two types of BHSs occur: cyanotic often called (cyanotic infantile syncope)without assystol and pallid often called (pallid infantile syncope or reflex anoxic seizures) with assystol

Benign paroxysmal vertigo Benign paroxysmal vertigo (BPV) manifests as sudden, brief overwhelming sensations of vertigo that cause child to stagger, lose balance, and sometimes fall. Thechild appears distressed and frightened and might become pale, diaphoretic, and nauseated. Nevertheless, consciousnessis maintained. An episode may last from a few minutes to several hours, and episodes may occur once every few months to several times per week. BPV is thought to be a migraine variant; there is often a family history of migraine. The disorder usually affects preschoolage children and usually resolves by 7 years of age, although most affected children go on to develop more typical migraine symptoms later in life. As opposed to other causes of vertigo, in BPV there is no accompanying tinnitus, hearing impairment, or other brainstem dysfunction, although nystagmus can be present. Diagnosis is aided by a normal EEG and neurologic examination. The lack of rhythmic movements or alteration of consciousness further differentiates BPV from epilepsy.

Pseudoseizures Pseudoseizures, also referred to as psychogenic seizures or simply nonepileptic seizures (to avoid a presumption of etiology or any pejorative connotation), are paroxysmal changes in motor activity or behavior that resemble epileptic seizures clinically but have no EEG correlate

Features suggestive of pseudoseizures are as The seizure occurs when the patient is observed, but not when alone follows: 1

The seizures are of gradual rather than of sudden onset

2

Uncontrolled flailing occurs, rather than true tonic–clonic movements

3

The seizure is accompanied by histrionics, with screaming and shouting

4

Painful stimuli are avoided during an attack

5

There is a sudden cessation of the seizure, with immediate return to an alert and responsive state

6

Seizures

DEFINITIONS A seizure is a clinical event in which there is a sudden disturbance of neurological function caused by an abnormal or excessive neuronal discharge. . An epileptic seizure is a paroxysmal alteration in behavior, motor function, or autonomic function or a combination of these, occurring in association with excessive synchronous neuronal activity in the central nervous system (CNS). in the absence of an acute cerebral insult has an incidence of about 0.05% (after the first year of life when it is more common) and a prevalence of 0.5%. This means that most large secondary schools will have about six children with an epilepsy of childhood or adolescence. Most epilepsy is idiopathic

Acute symptomatic seizures are seizures occurring in association with a transient acute structural or metabolic CNS insult A febrile convulsion is a seizure associated with fever in the absence of another cause and not due to intracranial infection from meningitis or encephalitis

Causes of seizures

Epilepsy Idiopathic (70-80%)  Secondary  Cerebral dysgenesis/malformation  Cerebral vascular occlusion  Cerebral damage, e.g. congenital infection, hypoxic-ischaemic encephalopathy, intraventricular  haemorrhage/ischaemia Cerebral tumour  Neurodegenerative disorders  Neurocutaneous syndromes 

Non-epileptic Febrile convulsions  Metabolic  Hypoglycaemia  Hypocalcaemia/hypomagnesaemia  Hypo/hypernatraemia  Head trauma  Meningitis/encephalitis  Poisons/toxins 

An international classification of epilepsy is used. This broadly classifies seizures as either: Generalised seizures may be: absence  myoclonic  tonic  tonic-clonic  astatic.  focal seizures will depend on the part of the brain where the discharge originates: Frontal seizures - involve the motor cortex. May lead to clonic movements, which may travel  proximally (Jacksonian march). Temporal lobe seizures, the most common of all the epilepsies - may result in strange warning  feelings or aura with smell and taste abnormalities and distortions of sound and shape.Lip smacking, plucking at one's clothing, and walking in a non-purposeful manner (automatisms) may be seen, Consciousness can be impaired . Occipital seizures - cause distortion of vision.  Parietal lobe seizures - cause contralateral dysaesthesias (altered sensation), or distorted body image.  Focal seizures are also delineated according to level of consciousness: simple partial focal seizures - consciousness is retained  complex partial focal seizures (dyscognitive seizure) - consciousness is lost.  partial focal seizures with secondary generalisation - focal seizure followed by generalised tonic-clonic  seizure.

Other Classification of Seizures Partial Seizures Simple partial seizures With motor signs With somatosensory With autonomic symptoms or signs With psychic symptoms Complex partial seizures Simple partial onset followed by impairment of consciousness, with or without automatisms With impairment of consciousness at the onset, with or without automatisms Generalized Seizures Absence seizures Myoclonic seizures Clonic seizures Tonic-clonic seizures Tonic seizures Atonic seizures Unclassified Epileptic Seizures Neonatal seizures Severe myoclonic epilepsy in infancy Epilepsy with continuous spike-and-wave patterns during slow-wave sleep Acquired epileptic aphasia (Landau-Kleffner syndrome) Special Syndromes Febrile convulsions Isolated seizures or isolated status epilepticus Acute symptomatic seizures: e.g., alcohol withdrawal seizures, eclampsia, uremia

Classification of Epilepsies and Epileptic Syndromes Generalized Epilepsies Idiopathic

Benign neonatal familial

Benign neonatal convulsions

Benign myoclonic epilepsy in infancy Juvenile absence epilepsy

Childhood absence epilepsy (pyknoepilepsy) Juvenile myoclonic epilepsy (janz syndroml)

Epilepsy with grand mal seizures upon awakening Other generalized idiopathic epilepsies that do not conform exactly to the syndromes just described

Cryptogenic West syndrome (infantile spasms)

Lennox-Gastaut syndrom

Epilepsy with myoclonic astatic seizures

Epilepsy with myoclonic absences

Symptomatic Early myoclonic encephalopathy

Specific disease states manifesting with seizures : e.g.,

alcohol withdrawal seizures, eclampsia, uremia Unclassified Epileptic Seizures

Neonatal seizures

Severe myoclonic epilepsy in infancy

Epilepsy with continuous spike-and-wave patterns during slow-wave sleep Acquired epileptic aphasia (Landau-Kleffner syndrome)

Localization-Related (Focal, Partial) Epilepsies

Click to edit the outline text format Benign childhood epilepsy with centrotemporal spikes(rolandic) Idiopathic

Childhood epilepsy with occipital paroxysms

Second Outline Level

Third Outline  Level The subclassification is determined by the anatomic location suggested Fourth Outline by the clinical history, predominant seizure type, interictal and ictal EEG, and imaging studies; thus, SPS, CPS, or secondarily Level generalized seizures arising from frontal lobes, parietal, temporal, Outline  occipital, multiple lobes or an unknown focusFifth Localization related Level but uncertain symptomatic or idiopathic Sixth  Outline Symptomatic





Scheme for Organizing Epileptic Conditions

With Generalized Seizures

With Partial (Focal) Seizures

Absence (petit mal) epilepsy Juvenile absence epilepsy generalized tonic-clonic Juvenile myoclonic epilepsy Benign neonatal seizures

Benign epilepsy with centrotemporal spikes (rolandic epilepsy) Childhood epilepsy with occipital spikes

Infantile spasms Lennox-Gastaut syndrome

Temporal lobe (psychomotor) epilepsy Epilepsies caused by gray matter heterotopias, polymicrogyria Epilepsies caused by focal postasphyxial gliosis

Febrile seizures Most toxic- and metabolicinduced seizures Many isolated tonic-clonic seizures Early post-traumatic seizures

Partial seizures occur when conditions with reactive seizures are superimposed on transient or preexisting nonepileptogenic brain injury, as often seen with head trauma, hypernatremia, hypoglycemia

Primary (idiopathic) epilepsies

Without structural lesions; benign; genetic

Secondary (symptomatic) epilepsies

With anatomic or known biochemical lesions

Conditions with reactive seizures

Abnormal reaction of an otherwise normal brain to physiologic stress or transient epileptogenic insult

Some epilepsy syndromes Generalised epilepsies Infantile spasms 4-6 month Violent flexor spasms of the head, trunk and limbs followed by extension of the arms (so-called 'salaam spasms'). Flexor spasms last 1-2 sec, often multiple bursts of 20-30 spasms, often on waking, but may occur many times a day. May be misinterpreted as colic. Social interaction often deteriorates - a useful marker in the history. Many causes, two-thirds have underlying neurological cause(symptomatic) with poor prognosis. The EEG shows hypsarrhythmia, a chaotic pattern of high-voltage slow waves, and multi-focal sharp wave discharges Treatment is with vigabatrin or corticosteroids, Good response in(cryptogenic) 30-40%, but side-effects are common. Most will subsequently lose skills and develop learning disability or epilepsy . Lennox-Gastaut syndrome 1-3 years Multiple seizure types, but mostly drop attacks (astatic seizures), tonic seizures and atypical absences. Also neurodevelopmental arrest or regression and behaviour disorder. Often other complex neurological problems or history of infantile spasms. slow wave EEG Prognosis is poor .

Typical (petit mal) absence seizures 4-12 years Stare momentarily and stop moving, may twitch their eyelids or a hand minimally. Lasts only a few seconds and certainly not longer than 30 seconds.Child has no recall except realises they have missed something and may look puzzled or say 'pardon' on regaining consciousness. Developmentally normal but can interfere with schooling. Accounts for only 2% of childhood epilepsy. Two-thirds are female. The episodes can be induced by hyperventilation, the child being asked to blow on a piece of paper or windmill for 2-3 minutes, a useful test in the outpatient clinic. The EEG shows generalised 3 per second spike and wave discharge, which is bilaterally synchronous during and sometimes between attacks . Prognosis is good with 95% remission in adolescence. 5-10% may develop tonic-clonic seizures in adult life Rx Na valoprat Ethuxonamide lomatragen. Juvenile myoclonic epilepsy (JANZ SYNDROM AD CH 6) Adolescence-adulthood Myoclonic seizures, but generalised tonic-clonic seizures and absences may occur, mostly shortly after waking. A typical history is throwing drinks or cornflakes about in the morning as myoclonus occurs at this time. Learning is unimpaired. Characteristic EEG generalized fast or poly spike. Response to treatment is usually good but lifelong with Na valoprate. A genetic linkage has been identified

Focal epilepsies syndrom Benign rolandic epilepsy, also known as benign childhood epilepsy with centrotemporal spikes (BCECTS) 4-10 years Tonic-clonic seizures in sleep, or simple partial seizures with awareness of abnormal feelings in the tongue and distortion of the face (supplied by the rolandic area of the brain). Comprises 15% of all childhood epilepsies. EEG shows focal sharp waves from the rolandic or centrotemporal area. Important to recognise as it is benign and does not always require treatment with good respond to carpemezepam. Almost all remit in adolescence. Benign occipital epilepsy 1-14 years Younger children - periods of unresponsiveness, eye deviation, vomiting and autonomic features. Older children - headache and visual disturbance including distortion of images and hallucinations. Uncommon. EEG shows occipital discharges.can treatedb with carpemezepam or Na valoprate Remit in childhood.

Investigation of seizures

EEG

An EEG is indicated whenever epilepsy is suspected. It is analysed to identify asymmetry, any focal abnormalities such as sharp waves or slowing that might suggest underlying abnormalities. Many children with epilepsy have a normal initial EEG; and many children who will never have epilepsy have EEG abnormalities. Unless a seizure is actually captured on the EEG it does no more than add supportive evidence (or not) for the diagnosis. If the standard EEG is normal, abnormalities may be better seen during sleep, so a sleep or sleep-deprived record can be helpful. Additional techniques are 24-hour ambulatory EEG or, ideally, video-telemetry. In assessment for surgery more invasive techniques such as subdural electrodes can be used.

Imaging Structural. MRI and CT brain scans are not required routinely for  childhood generalised epilepsies. They are indicated if there are neurological signs between seizures, or if seizures are focal, in order to identify a tumour, vascular lesion, or area of sclerosis which could be treatable. MRI FLAIR (fluid-attenuated inversion recovery) sequences better detect mesial temporal sclerosis in temporal lobe epilepsy. Functional scans. While it is not always possible to see structural lesions,  techniques have advanced to allow functional imaging to detect areas of abnormal metabolism suggestive of seizure foci. These include PET (positron emission tomography) and SPECT (single positron emission computed tomograpy), which use isotopes and ligands, injected and taken up by metabolically active cells. Both can be used between seizures to detect areas of hypometabolism in epileptogenic lesions. SPECT can also be used to capture seizures and areas of hypermetabolism. Blood tests and metabolic investigations may be warranted when there is developmental regression or seizures are related to feeds or fasting. GENERALIZED AND NON FEBRIL

Genetic studies will become increasingly helpful as certain epilepsy syndromes are now known to be due to genetic deletions causing abnormalities of sodium and other ion channels, the channelopathies

The diagnosis is primarily based on a detailed history from the child and eyewitnesses, substantiated by a video if available. Clinical examination should include checking the skin for neurocutaneous markers and a detailed neurological examination to identify any neurological abnormalities. Although epilepsy is usually idiopathic, it may be the presentation or a complication of an underlying neurological disorder

‘gold standard’ for distinguishing epileptic seizures from non-epileptic attack disorder (NEAD) is Video telemetry

This is the mainstay in managing epileptic seizures. Principles governing their use are: Not all seizures require anti-epileptic drug therapy. This decision should be based on the  seizure type, frequency and the social and educational consequences of the seizures against the possible unwanted effects of the drugs. Choose the appropriate drug for the seizure.  Inappropriate antiepileptics may be detrimental, e.g. ··carbamazepine·· can make absence and myoclonic seizures worse. . Monotherapy at the minimum dosage is the desired goal, although in practice several  drugs may be required. All anti-epileptic drugs (AEDs) have potential unwanted effects and these should be  discussed with the child and parent. Drug levels are not measured routinely but may be useful to check compliance or for  some drugs with erratic pharmacokinetics, e.g. ··phenytoin··. Patients who have had prolonged seizures are given rescue therapy to have with them.  This is usually a benzodiazepine, e.g. rectal ··diazepam·· or buccal midazolam. Anti-epileptic drug therapy can usually be discontinued after 2 years free of seizures. 

Other treatment options In children with intractable seizures there are a number of radical treatment options. Ketogenic (fat based) diets may be helpful in some children. Its mechanism of action is  poorly understood. Vagal nerve stimulation, delivered using externally programmable stimulation of a wire  implanted around the vagal nerve, may possibly be useful for focal seizures; trials are being conducted. Surgery. Cessation of seizures and drug therapy may be achieved in some children  whose clinical seizures are localised to a specific location in the brain as demonstrated on the EEG and functional imaging. The main procedure is temporal lobectomy for mesial temporal sclerosis but other procedures include hemispherectomy or hemispheric (does not involve hemisphere removal and problems with shifts in space) and focal resections. Detailed assessment is required to ensure that the benefits outweigh the risks

Management of Seizures Refractory to Medical Therapy Incorrect Diagnosis Review seizure type Complex partial seizures may be mistaken for absenc seizures Reflex epilepsy with uncontrolled precipitating factors, photosensitivity, reading epilepsy Repeat EEG with hyperventilation, photic stimulation, and sleep recording If results are negative, consider nonepileptic paroxysmal disorders or Psychogenic seizures Migraine Porphyria, hypoglycemia, hypocalcemia Continuing seizures: admit for video/EEG monitoring to record the event Inappropriate Medication Review anticonvulsant levels and Review seizure type A second AED may have caused a drop in the serum level of a first-line drug Phenobarbital and carbamazepine may exacerbate atypical absence and myoclonic seizures Drowsiness caused by phenobarbital and benzodiazepine may exacerbate tonic seizures Phenytoin often worsens thee myoclonus epilepsy syndromes

Noncompliance with Medication or Medical Advice Check AED levels; ask patient to record medication doses taken Check sleep habits, drug use; arrange review by social worker, psychiatrist Inability to cope with epilepsy and avoidance of precipitating factors (adolescence, low intelligence, dysfunctional home situation) Review all patient’s prescribed and over-the-counte medication; urine drug screen for drug abuseExacerbation by other medication or toxins Intercurrent Illness or Metabolic Complication of Another Medication Serum Na+, K+, glucose, Ca2+, Mg2+, creatinine, liver function studies, complete blood cell count, pregnancy test Intractable Epilepsies one third of cases of symptomatic focal epilepsy are refractory to current medical therapy After adequate attempt with two first-line medications and available new AEDs, refer for epilepsy surgery assessment Symptomatic generalized epilepsies such as West syndrome and Lennox-Gastaut syndrome are often refractory Need to reassess goals of therapy Refer for surgical assessment if there are recurrent falls caused by tonic or atonic seizures in older child Epilepsy with progressive neurologic deterioration: e.g., brain tumor, inherited disorders of metabolism, degenerative neurological disease, progressive myoclonus epilepsy, phakomatosis, systemic or cerebral vasculitis Review history, family history, and physical examination;

Indications for Anticonvulsant Serum Level Monitoring Introduction and stabilization of a patient on phenytoin

Alteration in seizure pattern or frequency A change in the dosage of an anticonvulsant

Commencement or withdrawal of other medications that interfere with anticonvulsants Symptoms of toxicity To check patient compliance

Choice of antiepileptic drugs (NICE, National Institute of Clinical Evidence, 2004)

Seizure type

First line

Second line

Tonic-clonic

Valproate,

,

Absence

Valproate,

Myoclonic

Valproate

Generalised epilepsies

Focal epilepsies

, valproate

, , , , , tiagabine, vigabatrin

Common or important side-effects of anti-epileptic drugs Valproate

Weight gain, hair loss

Carbamazepine/oxcarbazepine

Rash, neutropenia, hyponatraemia, ataxia Liver enzyme induction, can interfere with other medication

Vigabatrin

Restriction of visual fields, which has limited its use. Sedation

Lamotrigine

Rash

Ethosuximide

Nausea and vomiting

Topiramate

Drowsiness, withdrawal and weight loss

Gabapentin

Insomnia

Levetiracetam

Sedation

Benzodiazepines - clobazam, clonazepam diazepam, nitrazepam Sedation, tolerance to effect, increased secretions

NICE, National Institute of Clinical Evidence (EPLEPSY GUIDLINE)

Causes of Neonatal Seizures Ages 1-4 Days Hypoxic-ischemic encephalopathy Drug withdrawal,( maternal drug use of narcotic or barbiturates) Drug toxicity: (lidocaine, penicillin) Intraventricular hemorrhage

Acute metabolic disorders (Hypocalcemia ) Perinatal asphyxia,

Hypoglycemia Hypomagnesemia Hyponatremia or hypernatremia Iatrogenic or inappropriate antidiuretic hormone secretion Inborn errors of metabolism

Ages 4-14 Days Infection Meningitis (bacterial), encephalitis (enteroviral, herpes simplex) Metabolic disorders Hypocalcemia ( Diet, milk formula) Hypoglycemia, persistent Inherited disorders of metabolism: galactosemia, fructosemia, leucine sensitivity Hyperinsulinemic hypoglycemia Anterior pituitary hypoplasia, pancreatic islet cell tumor Beckwith syndrome Drug withdrawal, maternal drug use of narcotic or barbiturates Benign neonatal convulsions, familial and nonfamilial

Ages 2-8 Weeks Meningitis bacterial Herpes simplex or enteroviral , Head injury Subdural hematoma, child abuse Aminoacidurias, urea cycle defects, organic acidurias

Neonatal adrenoleukodystrophy Lissencephaly Focal cortical dysplasia Tuberous sclerosis Sturge-Weber syndrome

Febrile seizures (febrile convulsions)

These occur in 3% of children, between the ages of 6 months and 5 years. There is a genetic predisposition, with a 10% risk if the child has a firstdegree relative with febrile seizures. The seizure usually occurs early in a viral infection when the temperature is rising rapidly. The seizures are usually brief, and are generalised tonic-clonic seizures. 30% _40% will have further febrile seizures This is more likely in(recurrence) the younger the child, the shorter the duration of illness before the seizure, the lower the temperature at the time of seizure and if there is a positive family history. Simple febrile seizures do not cause brain damage and the child's subsequent intellectual performance is the same as children who do not experience a febrile seizure. There is a 1-2% chance of developing epilepsy, similar to the risk for all children. complex febrile seizures; i.e. those which are focal, prolonged, or

Examination should focus on the cause of the fever, which is usually a viral illness but a bacterial infection including meningitis should always be considered. The classical features of meningitis such as neck stiffness and photophobia may not be as apparent in children less than 18 months of age, so an infection screen (including blood cultures, urine culture and lumbar puncture for CSF) may be necessary. In the unconscious child (Glasgow Coma Scale 5 minutes), rescue therapy with rectal diazepam or buccal midazolam can be supplied. Oral prophylactic anti-epileptic drugs are not used as they do not reduce the recurrence rate of seizures or the risk of epilepsy. An EEG is not indicated as it does not serve as a guide for treatment nor does it predict seizure recurrence.

BENIGN FEBRILE SEIZURES ❏ most common cause of seizure in children ❏ 3-5% of all children, M > F Characteristics ❏ age 6 months - 6 years ❏ thought to be associated with initial rapid rise in temperature ❏ no neurologic abnormalities or developmental delay before or after seizure ❏ no evidence of CNS infection/inflammation before or after seizure ❏ no history of non-febrile seizures ❏ most common seizure type is brief generalized tonic-clonic Typical Febrile Seizure ❏ duration < 15 minutes (95% < 5 minutes) ❏ generalized, symmetric ❏ does not recur in a 24 hour period Atypical Febrile Seizure ❏ any of the following features • focal origin • > 15 minute duration, multiple (> 1 in 24 hours) • followed by transient neurologic deficit Risk Factors for Recurrence ❏ 33% chance of recurrence, most recur within 1 year ❏ age of onset < 1 year 50% chance of recurrence if < 1 year 28% chance of recurrence if > 1 year ❏ family history of febrile seizures or epilepsy ❏ low body temperature at time of seizure ❏ shorter duration of fever ( 90%, varies with serum protein concentration)

Free phenytoin = active phenytoin  (anticonvulsant and toxic effects)

Toxicity more likely with hypoalbuminemia  (usually if < 2 g/dL) Therapeutic levels  Total phenytoin: 10 - 20 mcg/ml Free phenytoin: 0.8 - 1.6 mcg/ml

 

Initial choice of long acting anticonvulsants in SE Is patient an infant? Is patient already receiving phenytoin? No

At high risk for extravasation ? (small vein, difficult access etc.)?

No

Phenytoin

Yes

Fosphenytoin

Yes

Phenobarbital

If SE persists Propofol infusion 5-10 mg/kg/hr after bolus 2  mg/kg Midazolam infusion 1 - 10 mcg/kg/min after  bolus 0.15 mg/kg Pentobarbital infusion 1-3 mg/kg/hr after  bolus 10 mg/kg Paraldehyde: no longer allowed for human  use Isoflurane 

Non - convulsive status epilepticus

How do you tell that patient’s seizures have  stopped?

Non - convulsive SE ? Neurologic signs after termination of SE are  common: Pupillary changes  Abnormal tone  Abnormal Babinski reflex Posturing  Clonus  May be asymmetrical 



HEAD INJURY

Skull fractures Linear skull fractures are the most common pediatric skull fracture, occurring in nearly 75% of the cases. The parietal bone is the most common fracture site. Accidental linear fractures rarely cross suture lines. Normal variations of the pediatric skull and suture lines are often misinterpreted as fractures. . ‗Growing fractures‘ are a variation of linear fractures that are unique to pediatrics. . Depressed skull fractures are due to direct, forceful impact and may be associated with concomitant underlying brain lacerations. They can be difficult to diagnose with one radiological view, and may require oblique views for diagnosis. Early referral to a neurosurgical team is essential, as the definitive management of a depressed skull fracture may involve operative elevation of the depressed fragment of bone. Routineprophylactic antibiotics are not recommended. Basilar skull fractures should be suspected in patients with the appropriate clinical signs such as hemotympanum, Battle sign, racoon eyes, nasal blood or nasal CSF leak. CT scan best diagnoses such fractures, although this test is imperfect Management generally includes neurosurgical consultation and symptomatic care. Often, no intervention is necessary. Antibiotic prophylaxis is not routinely

Cerebrovascular disease

Cerebral haemorrhage

Extradural haemorrhage

This usually results from arterial or venous bleeding into the extradural space following direct head trauma. It is usually associated with a skull fracture. In young children there is often a lucid interval until the conscious level deteriorates and seizures occur due to the enlarging haematoma acting as a space-occupying lesion. There may be focal neurological signs with dilatation of the ipsilateral pupil, paresis of the contralateral limbs and a false localising uni- or bilateral VIth nerve paresis. In young children, initial presentation may be with anaemia and shock. The diagnosis is confirmed with a CT scan. Management is to correct hypovolaemia. Surgical evacuation of the haem-atoma and arrest of the bleeding may be required and can be urgent in some situations.

Acute epidural hematoma and midline shift

Concave shape

Subdural haematoma

This results from tearing of the veins as they cross the subdural space. It is a characteristic lesion in non-accidental injury caused by shaking or direct trauma in infants or toddlers. Retinal haemorrhages are usually present. There has been recent controversy surrounding the relative contributions of direct trauma, shearing injury and hypoxia. Subdural haematomas are occasionally seen following a fall from a considerable height.

Subdural Hematoma Convex shape

Subarachnoid haemorrhage

This is much more common in adults. Presentation is usually with acute onset of head pain, neck stiffness and occasionally fever. Retinal haemorrhage is usually present. Seizures and coma may develop. A CT scan of the head usually identifies blood in the CSF. A lumbar puncture in the acute situation is best avoided as haemorrhage may extend following the release of intracranial pressure. The cause is often an aneurysm or arterio-venous malformation (AVM). It can be identified on MR angiography (MRA) or CT or conventional angiography. Treatment can be neurosurgical or with interventional radiography.

Stroke in childhood Strokes occur not only in adults but also in infants, and children. They originate from vascular, thromboembolic(neonate) and haemorrhagic pathology. The clinical signs such as hemiplegia or speech or visual disturbance depend on the vascular territory compromised. Compromise of the anterior circulation (internal carotid, anterior and middle cerebral arteries) is more common than of the posterior circulation (vertebrobasilar arteries). Causes include thrombotic: cardiac - congenital cyanotic heart disease, e.g. Fallot's tetralogy, endocarditis  haematological - sickle cell disease;  deficiencies of anti-thrombotic factors, e.g. protein C metabolic – homocystinuria, . MELAS (myoclonic epilepsy, lactic acidosis and stroke) . post varicella or other viral infections. Haemorrhagic vascular malformations - moyamoya disease. These children have abnormal vasculature. Moyamoya

inflammatory - damage to vessels in autoimmune disease, e.g. SLE menengitis  I.



investigations include brain imaging with CT and MRI, and Vasculature can be assessed with CT and MR angiography. haematological tests for thrombophilia and metabolic tests. Cardiological tests include echocardiography and carotid Doppler studies. More subtle vascular changes still require formal angiography Long-term rehabilitation, with multi-collaborative working, may be required. Prophyl-axis with aspirinl " may be given but further evidence is needed on the advisability of anti-thrombolytic agents

A, Cranial computed tomographic scan reveals hyperdense area in left temporal lobe (arrowheads) representing intraparenchymal hemorrhage. B, Cerebral angiography shows lobulated representing the mycotic aneurysm, most probably residing in the middle cerebral artery tree(arrows). C, Anteroposterior angiographic view confirms the location of the aneurysm in the middle cerebral artery (straight arrows) located laterally rather than the more medial anterior cerebral artery (curved arrows). The internal carotid artery (open arrows) gives rise to both the anterior and the middle cerebral arteries

Cranial computed tomographic scan of a 3month-old boy with trisomy 21 and tetralogy of Fallot who, after cardiac catheterization, had focal seizures involving the right side of the face and right arm. Region of hypodensity in left hemisphere (arrowheads) reflects infarction of the left middle cerebral artery territory, most likely caused by embolic occlusion of that vessele

Neuroradiologic, Laboratory, and Cardiovascular Assessment of Stroke in Children Neuroradiologic Assessment Rapid detection of intracranial blood Cranial CT Cranial MRI (also detects extravascular blood but is not as rapidly obtained as cranial CT images) Detection of brain parenchymal changes related to stroke Cranial MRI, including diffusion weighted imaging Cranial CT (reveals changes later in course than MRI) Detection of abnormal vascular structure Percutaneous cerebral angiogram (provides the most complete and accurate demonstration of extracranial and intracranial vasculature) Cranial MRA

Laboratory Assessment Disturbance of RBC, WBC, or platelet number Hematocrit Platelet count WBC count with differential Disturbance of coagulation PT, PTT Antithrombin III level Protein C level, protein S level Lupus anticoagulant detection, anticardiolipin antibody, antiphospholipid AB Metabolic disturbances Serum electrolytes, glucose Serum amino acids Urine organic acids Serum/CSF lactate and pyruvate and Urine toxic screen Disturbance of hemoglobin Hemoglobin concentration Hemoglobin electrophoresis Inflammatory disturbances ESR ANA, RF CSF studies: glucose, protein, cell counts, special stains, cultures Lipid and lipoprotein disturbances Serum triglycerides Serum cholesterol; if high, obtain fasting HDL Cardiovascular Assessment ECG Standard and transesophageal echocardiogram and doppler carotide US

COMA

Clinico-Anatomical Correlation of Disorders of Cranial Nerve II and Afferent Visual Pathways Anatomical Location

Visual Phenomena

Other Neurological and Medical Findings

Possible Etiologies

Retina

Transient monocular visual loss

Hollenhorst's plaque

Carotid disease, giant cell arteritis, migraine, vasospasm, cardiac emboli

Acute monocular visual loss

Cherry-red spot, box-carring

Central retinal artery occlusion

Subacute monocular visual loss

Retinal hemorrhage, cotton wool spots, dilated retinal veins

Central retinal vein occlusion

Subacute monocular visual loss

Vitreous opacification

Vitreous hemorrhage

Impaired visual acuity

Metamorphopsia

Central serous chorioretinopathy, macular degeneration

Optic nerve

Ipsilateral visual loss (decreased acuity, decreased color vision, central scotoma, altitudinal field defect)

Optic atrophy, optic disc swelling

Optic neuritis, ischemic optic neuropathy, compressive lesions

Optic chiasm

Bitemporal hemianopsia, decreased acuity and color vision

Optic atrophy

Pituitary adenoma, craniopharyngioma, optic glioma, meningioma, aneurysm

Optic tract

Contralateral incongruous homonymous hemianopia

Contralateral relative afferent pupillary defect, ―bowtie‖ optic atrophy

Pituitary adenoma, craniopharyngioma, aneurysm

Optic radiations

Contralateral homonymous hemianopia

Preserved visual acuity, intact pupillary response, decreased OKN to side of lesion, sensory loss, hemiparesis

MCA stroke, temporal or parietal mass lesion

Occipital lobe

Contralateral congruous homonymous hemianopia (with or without macular sparing), quadrantic field defect, homonymous hemianopic central scotoma, cortical blindness (if bilateral)

Usually isolated deficits

PCA stroke, migraine, Alzheimer's, hypertensive encephalopathy

The 'floppy infant' Causes of the floppy infant Cortical Hypoxic-ischaemic encephalopathy Cortical malformations Genetic Down's syndrome Prader-Willi syndrome Metabolic Hypothyroidism Hypocalcaemia Neuromuscular Spinal muscular atrophy Myopathy Myotonia Myasthenia gravis

The Evaluation of the Hypotonic Infant Measurers of hypotonia: (A) pull to sit, (B) scarf sign, (C) shoulder suspension, and (D) ventral suspension

Clinical Evaluation Localization of Hypotonia Central Hypotonia Systemic Diseases Syndromic Central Hypotonia Nonsyndromic Central Hypotonia With Cerebral Dysgenesis or Grossly Normal Brain With Delayed Myelination or Without Delayed Myelination

Hypotonia Caused by Craniocervical Junction Lesions(trauma) Motor Unit Hypotonia Peripheral Nerve Anterior Horn Cell Neuromuscular Junction Muscle

Persisting hypotonia in infants can be readily felt on picking up the infant, who tends to slip through the fingers or hang like a rag-doll when suspended prone. There will be marked head lag when the head is lifted by the arms from supine. The clinical examination can help determine the site of the lesion, whether cortical or neuromuscular. Central hypotonia is associated with poor truncal tone but preserved limb tone. Dysmorphic features suggest a genetic cause. Lower motor neurone lesions are suggested by a frog-like posture , poor anti-gravity movements and absent reflexes.

Neuromuscular disorders Any part of the lower motor pathway can be affected in a neuromuscular disorder, so that anterior horn cell disorders, peripheral neuropathies, disorders of neuromuscular transmission and primary muscle diseases can all occur. The causes of neuromuscular disorders are shown in The key clinical feature of a neuromuscular disorder is weakness, which may be progressive or static. Affected children may present with: floppiness  delayed motor milestones  muscle weakness  unsteady/abnormal gait  fatiguability.  The first step is to decide on the site of the lesion. History and examination provide useful clues. Children with myopathy often show the waddling gait suggestive of proximal muscle weakness. More severe weakness results in Gowers' sign. This is the need to turn prone to rise to a standing from a supine position. This is normal until the age of 3 years. It is only when children have become very weak that they 'climb up the legs with the hands' to gain the standing position . A pattern of more distal wasting and weakness, particularly in the presence of pes cavus, suggests an hereditary motor sensory neuropathy. Increasing fatiguability through the day, often with ophthalmoplegia and ptosis, would be more consistent with depletion at the motor end-plate and a diagnosis of myasthenia gravis. It is usually difficult to differentiate a myopathy from a neuropathy on clinical grounds but there are some broad points to look for: Anterior horn cell - there are signs of denervation: weakness, loss of reflexes, fasciculation and wasting as the  nerve supply to the muscle fails. Neuropathy - often distal nerves affected. There is weakness, loss of reflexes, sensory loss and temperature  change as nerve supply fails. Myopathy - there is weakness, wasting, gait changes as muscle structure is affected. Reflexes initially intact.  Often more proximal weakness. Neuromuscular junction - as end-plate acetylcholine stores become depleted, there is diurnal worsening through  the day leading to fatiguability.

Investigations These depend on the clinical decision regarding the site of lesion. Myopathy (EMG SHOW LOW ACTION POTIONTAL): serum creatine phosphokinase - markedly elevated in Duchenne's and Becker's  muscular dystrophy muscle biopsy, needle or open - modern histochemical techniques often enable a  definitive diagnosis ultrasound and MRI of muscles - used in specialist centres to diagnose and monitor  progress DNA testing - to identify abnormal genes.  Neuropathy: nerve conduction studies - to identify delayed motor and sensory nerve conduction  velocities seen in neuropathy DNA testing - for abnormal genes  nerve biopsy - rarely performed  EMG (electromyography) helps in differentiating myopathic from neuropathic  disorders, e.g. fatiguability on repetitive nerve stimulation in myasthenia. However, it should be used selectively in children, as the nerve conduction studies cause a tingling sensation and electromyography requires insertion of fine needle electrodes. Diagnosis of neuromuscular disorders has been made easier by the advances made in confirmatory DNA tests for many of them, e.g. spinal muscular atrophy (SMA), Duchenne's muscular dystrophy, myotonic dystrophy, hereditary neuropathies. This also allows antenatal testing and genetic counselling and often obviates the need for the discomfort of peripheral neurophysiology.

Disorders of the anterior horn cell

Spinal muscular atrophy This disorder is usually autosomal recessive, and due to degeneration of the anterior horn cells, leading to progressive weakness and wasting of skeletal muscles. This is the second most common cause of neuromuscular disease in the UK after Duchenne's muscular dystrophy. Spinal muscular atrophy type 1 (Werdnig-Hoffmann disease) A very severe progressive disorder presenting in early infancy (Diminished fetal movements are often noticed during pregnancy and there may be arthrogryposis (positional deformities of the limbs with contractures of at least two joints) at birth. Typical signs include: lack of antigravity power in hip flexors  absent deep tendon reflexes  intercostal recession  fasciculation of the tongue.  These children never sit unaided. Death is from respiratory failure by about 12 months of age. There are milder forms of the disorder with a later onset. Children with type 2 spinal muscular atrophy can sit, but never walk independently. Those with type 3 (Kugelberg-Welander) do walk and can present later in life.

Peripheral neuropathies The hereditary motor sensory neuropathies (HMSN)

This group of disorders typically leads to symmetrical, slowly progressive muscular wasting which is distal rather than proximal. Type I, formerly known as peroneal muscular atrophy (Charcot-Marie-Tooth disease), is usually dominantly inherited and the most common. Affected nerves may be hypertrophic due to demyelination followed by attempts at remyelination. Nerve biopsy typically shows 'onion bulb formation' due to these two processes. Onset is in the first decade with distal atrophy and pes cavus, the legs being affected more than the arms. Rarely, there may be distal sensory loss and the reflexes are diminished. The disease is chronic and only rarely do those affected lose the ability to walk. The initial presentation of Friedreich's ataxia can be similar

Acute post-infectious polyneuropathy (Guillain-Barré syndrome) Presentation is typically 2-3 weeks after an upper respiratory tract infection or campylobacter gastro-enteritis. There may be fleeting abnormal sensory symptoms in the legs, but the prominent feature is an ascending symmetrical weakness with loss of reflexes and autonomic involvement. Sensory symptoms, usually in the distal limbs, are less striking than the paresis but can be unpleasant. Involvement of bulbar muscles leads to difficulty with chewing and swallowing and the risk of aspiration. Respiratory depression may require artificial ventilation. The maximum muscle weakness may occur only 2-4 weeks after the onset of illness. Although full recovery may be expected in 95% of cases, this may take up to 2 years. The CSF protein is characteristically markedly raised, but this may not be seen until the second week of illness. The CSF white cell count is not raised. Nerve conduction velocities are reduced. Management of post-infectious polyneuropathy is supportive, particularly of respiration. Cortico-steroids have been shown to have no beneficial effect or may even delay recovery. The disorder is probably due to the formation of antibody attaching itself to protein components of myelin. Controlled trials have shown that the ventilator-dependent period can be significantly reduced by immunoglobulin infusion. If this is not successful, consider using plasma exchange

Bell's palsy is an isolated lower motor neuron paresis of the VIIth cranial nerve leading to facial weaknes. Although the aetiology is unclear in Bell's palsy, it is probably post-infectious with an association with herpes simplex virus in adults. Corticosteroids may be of value in reducing oedema in the facial canal during the first week. Recovery is complete in the majority of cases but may take several months. The main complication is conjunctival infection due to incomplete eye closure on blinking. This may require the eye to be protected with a patch or even tarsorrhaphy.

There are several other causes of facial nerve palsy. If symptoms of an VIIIth nerve paresis are also present then the most likely diagnosis is a compressive lesion in the cerebellopontine angle. The herpes virus may invade the geniculate ganglion and give painful vesicles on the tonsillar fauces and external ear, along with a facial nerve paresis. Treatment for this is with aciclovir. Hypertension should be excluded, as there is an association between Bell's palsy and coarctation of the aorta. If the facial weakness is bilateral, sarcoidosis should be suspected, but this is also seen in Lyme disease

Myasthenia gravis This presents as abnormal muscle fatiguability which improves with rest or anticholinesterase drugs Juvenile myasthenia This is similar to adult autoimmune myasthenia and is due to binding of antibody to acetylcholine receptors on the post-junctional synaptic membrane. This gives a reduction of the number of functional receptors. Presentation is usually after 10 years of age with ophthalmoplegia and ptosis, loss of facial expression and difficulty chewing). Generalised, especially proximal, weakness may be seen. Diagnosis is made by observing improvement following the administration of intravenous edrophonium and can be further confirmed by testing for acetylcholine receptor antibodies (seen in 60-80%). Treatment is with the use of anti-cholinesterases such as neostigmine or pyrido-stigmine. In the longer term, immunosuppressive therapy with prednisolonel " or azathioprinel " has been shown to be of value. Plasma exchange is used for crises. Thymectomy is considered if a thymoma is present or if the response to medical therapy is unsatisfactory. About a quarter will show remission post thymectomy and up to half show some improvement.

Muscle disorders The muscular dystrophies This is a group of inherited disorders with muscle degeneration, often progressive.

Duchenne's muscular dystrophy This is the most common muscular dystrophy, affecting 1 in 4000 male infants. It is inherited as an Xlinked recessive disorder, although about a third are new mutations. It results from a deletion of chromosome material on the short arm of the X chromosome (at the Xp21 site). This site is now known to code for a protein called dystrophin which maintains the integrity of the muscle cell wall. Where it is deficient, there is an influx of calcium ions, a breakdown of the calcium calmo-dulin complex and an excess of free radicals. These lead eventually to irreversible destruction of the muscle cells. The serum creatine phosphokinase (CPK) is markedly elevated. Some countries, e.g. Wales, have introduced neonatal screening for Duchenne's dystrophy so that affected children are detected in the neonatal test by an elevated CPK. Children present with a waddling gait or language delay and have to mount stairs one by one. Although the average age of diagnosis remains 5.5 years, children often become symptomatic much earlier. There may be selective atrophy of muscle, in particular of the sternal head of the pectoralis major and brachioradialis. There is pseudohypertrophy of the calves because of replacement of muscle fibres by fat and fibrous tissue. In the early school years, affected boys just tend to be slower and more clumsy than their peers. The progressive muscle atrophy and weakness means that they are no longer ambulant by the age of about 10-14 years. Death ensues in the late teens or twenties from respiratory failure or the associated cardiomyopathy. About a third of affected children have learning difficulties. Scoliosis is a common complication.

Management Appropriate exercise helps to maintain muscle power and mobility and delays the onset of scoliosis. Contractures, particularly at the ankles, should be prevented by passive stretching and the provision of night splints. Walking can be prolonged with the provision of orthoses, in particular those which allow ambulation by the child leaning from side to side. Lengthening of the Achilles tendon may be required to facilitate ambulation. Attention to maintaining a good sitting posture helps to minimise the risk of scoliosis. Scoliosis is managed with a truncal brace, a moulded seat and occasionally surgical insertion of a metal rod into the spine. Later in the illness, episodes of nocturnal hypoxia secondary to weakness of the intercostal muscles may present with lassitude or irritability. Respiratory aids, particularly overnight CPAP (continuous positive airway pressure) or non-invasive positive pressure ventilation (NIPPV), may be provided to improve the quality of life. As with all chronic disabling conditions, parent self-help groups are a useful continuing source of information and support for families. Affected children should be reviewed periodically at a specialist regional centre. Ambulant children with Duchenne's dystrophy are increasingly treated with corticosteroids (predni-solone for 10 days per month) to preserve mobility and prevent scoliosis. The precise mechanism by which glucocorticoids may increase strength in Duchenne's dystrophy is not known but their potential beneficial effects include inhibition of muscle proteolysis, a stimulatory effect on myoblast proliferation, an increase in myogenic repair, an antiinflammatory/immunosuppressive effect, reduction of cytosolic calcium concentrations and upregulation of utrophin, and alteration in skeletal muscle gene expression. It may be possible to identify female carriers if they have a mildly raised CPK or if the gene deletion can be detected on DNA analysis. Antenatal diagnosis is then possible.

Becker's muscular dystrophy

In Becker's dystrophy some functional dystrophin is produced. The features are similar to those of Duchenne's dystrophy but clinically the disease progresses more slowly. The average age of onset is 11 years, inability to walk in the late twenties, with death in the early forties, although this is very variable. Some staining for dystrophin is seen on muscle biopsy compared to biopsies from children with Duchenne's, where there is none

Congenital muscular dystrophies

This is a heterogeneous group of disorders, most with recessive inheritance, which present with muscle weakness at birth or early infancy. Typically the proximal weakness is slowly progressive with a tendency to contracture when the ability to walk is lost. Some may run a more static course . Biopsy shows dystrophic features with a reduction of spec-ific proteins such as merosin. These dystrophies may be linked with central nervous abnormalities which may result in learning difficulties

The inflammatory myopathies DERMATOMYSTITIS This is assumed to be a post-viral phenomenon as it often follows an upper respiratory tract infection and runs a self-limiting course. Pain and weakness occur in affected muscles. CPK is usually raised. This is a systemic illness, probably due to an angiopathy. Usual onset is between 5 and 10 years. This can be acute, but more typically is insidious with fever, misery, and eventually symmetrical muscle weakness, which is mainly proximal. Sometimes pharnyngeal muscle involvement affects swallowing. There is also a characteristic violaceous (heliotrope) rash to the eyelids, and peri-orbital oedema ). The rash may also affect the extensor surfaces of joints, e.g. elbow, and with time subcutaneous calcification can appear. Inflammatory markers (CRP, ESR) can be raised but not invariably. Muscle biopsy shows an inflammatory cell infiltrate and atrophy. Physiotherapy is needed to prevent contractures. Corticosteroids are the standard treatment, and continue at a tailored dose for 2 years. Other immunosuppressants, e.g. methotrexate, ciclosporin, may be needed. Mortality is 5-10%.

Myotonic disorders

Myotonia is delayed relaxation after sustained muscle contraction. It can be identified clinically and on electromyography. . This relatively common illness is dominantly inherited and caused by a nucleotide triplet repeat expansion, so this means there can be anticipation through generations, especially when maternally transmitted. Newborns can present with hypotonia and feeding and respiratory difficulties due to muscle weakness. It is then useful to examine the mother for myotonia. This manifests as slow release of handshake or difficulty releasing the tightly clasped fist. This may be mild and not have been appreciated. Sensitivity is required as diagnosis in the neonate may have repercussions for the family. Older children can present with myopathic facies learning difficulties and myotonia. Adults develop cataracts and males develop baldness and testicular atrophy. Death is usually due to cardiomyopathy.

Metabolic myopathies

Metabolic conditions can affect muscles, due either to the deposition of storage material or to energy-depleting enzyme deficiencies. Presentation is as a floppy infant or, in older children, with muscle weakness or cramps on exercise. The main causes are: Glycogen storage disorders  Disorders of lipid metabolism. Fatty acids are important muscle fuel. Fatty acid oxidation occurs in the mitochondria and defects in this pathway can result in weakness. Carnitine is essential to supply long-chain fatty acids to the mitochondria for breakdown, and carnitine deficiency causes weakness. Mitochondrial cytopathies - rare disorders which are coded as maternally inherited mitochondrial DNA. Myopathy may be the major manifestation or the disorder may be multisystem, with lactic acidosis and encephalopathy. Mitochondrial DNA testing is available

Congenital myopathies

These present at birth or in infancy with generalised hypotonia and muscle weakness. The names describe the changes seen on muscle biopsy or electron microscopy. They include: nemaline rod myopathy  central core disease  congenital fibre-type disproportion.  Creatine phosphokinase levels are normal or only mildly elevated

The neurocutaneous syndromes

The nervous system and the skin have a common ectodermal origin. Embryological disruption causes syndromes involving abnormalities to both systems - the neurocutaneous syndromes

Neurofibromatosis type 1 (NF1) This affects 1 in 3000 live births. It is an autosomal dominant, highly penetrant condition. One third are new mutations. The gene has been identified. In order to make the diagnosis, two or more of these criteria need to be present: six or more café-au-lait spots >5 mm in size before puberty, >15 mm after  puberty more than one neurofibroma, an unsightly firm nodular overgrowth of any  nerve axillary freckles  optic glioma which may cause visual impairment  one Lisch nodule, a hamartoma of the iris seen on slit-lamp examination  bony lesions from sphenoid dysplasia which can cause eye protrusion  first-degree relative with NF1.  The cutaneous features tend to become more evident after puberty, and there is a wide spectrum of involvement from mild to severe. Neurofibro-mata appear in the course of any peripheral nerve, including cranial nerves. They may look unsightly or cause neurological signs if they occur at a site where a peripheral nerve passes through a bony foramen. Visual or auditory impairment may result if there is compression of the IInd or VIIIth cranial nerve. Megalencephaly with learning difficulties and epilepsy are sometimes seen MRI SHOW HYPERINTENSE AREA IN B GANGLION AND INT CAPSULE.

Neurofibromatosis – numerous neurofibromas in an adult

Neurofibromatosis – plexiform neurofibroma on chin; also note the café au lait macules on the neck

Café au lait macule – associated with neurofibromatosis

Lisch nodule

Neurofibromatosis type 2 (NF2; bilateral, acoustic or central) is less common and presents in adolescence. Bilateral acoustic neuromata are the predominant feature and present with deafness and sometimes a cerebellopontine angle syndrome with a facial (VIIth) nerve paresis and cerebellar ataxia. There may be an overlap between the features of NF1 and NF2. Both NF1 and NF2 can be associated with endocrinological disorders, the multiple endocrine neoplasia syndromes (MENS).

Other associations are phaeochromocytoma, pulmonary hypertension, renal artery stenosis with hypertension, and gliomatous change, particularly in central nervous system lesions. Rarely, the benign tumours undergo sarcomatous change. However, most people with the disorder carry no features other than the cutaneous stigmata CT show glimatouse change.

Tuberous sclerosis This disorder is a dominantly inherited disorder but up to 70% are new mutations. Prevalence is 1 in 9000 live births. The cutaneous features consist of: depigmented 'ash leaf'-shaped patches which fluoresce under ultraviolet light roughened patches of skin (shagreen patches) usually over the lumbar spine  adenoma sebaceum (angiofibromata) in a butterfly distribution over the bridge of the nose  and cheeks, which are unusual before the age of 3 years Neurological features are: infantile spasms and developmental delay  epilepsy - often focal  intellectual impairment.  These children have severe learning difficulties and often have autistic features to their behaviour when older. Other features are: fibromata beneath the nails (subungual fibromata)  dense white areas on the retina (phakomata) from local degeneration  rhabdomyomata of the heart which are identifiable in the early weeks on echocardiography  but often resolve polycystic kidneys.  As with neurofibromatosis, gliomatous change can occur in the brain lesions. Many people who carry the gene have no stigmata other than the cutaneous features and no associated neurological features. CT scans will detect the calcified subependymal nodules and tubers from the second year of life. MRI is more sensitive and more clearly identifies other tubers and lesions.

Tuberous sclerosis – shagreen patch on lower back

Tuberous sclerosis – hypopigmented macules

Sturge-Weber syndrome This is a sporadic disorder with a haemangio-matous facial lesion (a port-wine stain) in the distribution of the trigeminal nerve associated with a similar lesion intracranially. The ophthalmic division of the trigeminal nerve is always involved . Calcification of the gyri causes characteristic 'rail-road track' calcification on skull X-ray. CT show hypoperfusion and calcification In the most severe form, it may present with epilepsy, learning disability and hemiplegia. Children presenting with intractable epilepsy in early infancy may benefit from hemispherectomy. For children who are less severely affected, deterioration is unusual after the age of 5 years, although there may still be seizures and learning difficulties. There is a risk of glaucoma

Sturge- Weber syndrome in which the distribution involves both the 1st and 2nd branch of the trigeminal nerve. Note the glaucoma of the right eye. In Sturge-Weber syndrome, lesions stop at the midline. When extensive facial involvement is present, there may be an associated glaucoma (buphthalmos). As this is one of the neurocutaneous syndromes, a CT scan of the head should be done to exclude intracranial involvement. Radiographs of the skull may reveal unilateral curvilinear, double-contoured lines of calcification in the cerebral cortex (―railroad track calcification‖). The intracerebral vascular abnormalities lead to brain atrophy and ocular lesions (optic atrophy

Neurodegenerative disorders

These are disorders that cause a deterioration in motor and intellectual function. Abnormal neurological features develop including seizures, spasticity, abnormal head circumference (macro- or microcephaly), involuntary movement disorders, visual and hearing loss and behaviour change. While individually rare, they are numerous and include: Lysosomal storage disorders, e.g. lipid storage disorders and mucopolysaccharidoses  in which absence of an enzyme leads to accumulation of a harmful metabolite. Peroxisomal enzyme defects, e.g. X-linked adrenoleucodystrophy. Peroxisomes are  catalase- and oxidase-containing organelles involved in long-chain fatty acid oxidation. Enzyme deficiencies can lead to accumulation of very long-chain fatty acids (VLCFAs). Heredodegenerative disorders, e.g. Huntington's disease, which presents with  progressive dystonia, dementia, seizures and corticospinal tract signs. Wilson's disease, from the accumulation of copper, may cause changes in behaviour  and additional involuntary movements or a mixture of neurological and hepatic symptoms. Subacute sclerosing panencephalitis (SSPE), a delayed response in adolescence to  previous measles infection causing neurological regression with a characteristic EEG, but has become rare since measles immunisation

CNS INFECTION

NORMAL CSF Normal Cerebrospinal Fluid (CSF) Constituents Substance

Plasma

CSF

Sodium (mEq/L)

140.0

144.0

Potassium (mm/L)

4.6

2.9

Magnesium (mEq/L)

1.6

2.2

Calcium (mg/dL)

8.9

4.6

Chloride (mEq/L)

99.0

113.0

Bicarbonate (mm/L)

26.8

23.3

Inorganic phosphate (mg/dL)

4.7

3.4

Protein (g/dL)

6.8

0.028 (28mg/dL)(15_40)

Glucose (mg/dL)

110.0

50 to 80 >50%of blood suger

Osmolality

0.3

0.29

pH

7.4

7.3

Pco2 (mmHg)

41.1

50.

Selected Disorders and Associated CSF Studies Domain

Disorder

Useful CSF Studies

Expected Results

Comments

Meningitis (purulent)

pr, gl, cell cts, gs, cx, op

↑ pr, ↓ gl, ↑ CSF PMNs, + gs and cx, + bacterial ag's, ↑ op + PCR

+ cryptococcal ag and india ink in cryptococcal meningitis

↑ LA

Mononuclear cells possible in partially rx'd bacterial meningitis

Cerebral Dysfunction Infectious

Meningitis (aseptic)

pr, gl, cell cts

↑ pr, nl gl, ↑ CSF WBC (10 to 1000 mononuc cells/mm3)

PMNs possible in early aseptic meningitis

Encephalitis

pr, gl, cell cts, gs, cx

mildly ↑ pr (50 to 100mg/dL), nl gl, ↑ CSF WBC 50 to 100/mm3 (mononuc)

Herpes simplex encephalitis

↑ RBC/xanthochromia, + CSF PCR HIV encephalopathy

pr, gl, cell cts

mildly ↑ pr, nl gl, nl or few WBC

Neurosyphilis (acute)

VDRL, pr, gl

↑ pr (>45mg/dL), ↑ WBC (5 to 500 mononuc/mm3), + VDRL

CSF parameters may be normal

Tuberculous meningitis

pr, gl, cell cts, op, acid-fast stain, cx

↑ pr (100 to 200mg/dL), ↓ gl (6 years Neisseria meningitidis Streptococcus pneum

Presentation The clinical features are listed in The early signs and symptoms of meningitis are non-specific, which makes early diagnosis difficult. Infants and young children may present with any combination of fever, poor feeding, vomiting, irritability, lethargy, drowsiness, seizures or reduced consciousness. A bulging fontanelle, neck stiffness and the infant lying with an arched back (opisthotonos) are late signs. Children old enough to talk are likely to describe the classical meningitis symptoms of headache, neck stiffness and photophobia. Neck stiffness may also be seen in some children with tonsillitis and cervical lymphadenopathy. As children with meningitis may also be septicaemic, signs of shock, such as tachycardia, prolonged capillary refill time, oliguria and hypotension, should be sought. Purpura in a febrile child of any age should be assumed to be due to meningococcal sepsis, even if the child does not appear unduly ill at the time; meningitis may or may not be present.

Investigations . A lumbar puncture is performed to obtain CSF to confirm the diagnosis, identify the organism responsible, and its antibiotic sensitivity. If any of the contraindications listed in are present, a lumbar puncture should not be performed, as under these circumstances the procedure carries a risk of coning of the cerebellum through the foramen magnum. If necessary, a lumbar puncture can be performed once the child's condition has stabilised. Although by this stage the organism will rarely be grown, the cytological and biochemical abnormalities of bacterial meningitis will still be present for several days after starting treatment. Even without a lumbar puncture, bacteriological diagnosis can be achieved in at least 50% of cases from the blood by culture, rapid antigen screen ig G and ig M or PCR. A throat swab should also be taken. Scrapings from a purpuric skin lesion may also be cultured. A serological diagnosis can be made on convalescent serum 4-6 weeks after the presenting illness

Management

It is imperative that there is no delay in the administration of antibiotics and supportive therapy in a child with meningitis. The choice of antibiotics will depend on the likely pathogen. A third-generation cephalosporin, e.g. cefotaxime or ceftriaxone, is the preferred choice to cover the most common bacterial causes. Although still rare in the UK, pneumococcal resistance to penicillin and cephalosporins is increasing rapidly in certain parts of the world. Whilst waiting for the sensitivity of pneumococcal cultures, rifampicin or vancomycin may be added. Ampicillin with chloramphenicol is an alternative in certain countries where thirdgeneration cephalosporins are not available, but resistance to these drugs means that they cannot be relied upon when used as single agents. Below 3 months of age, ceftriaxone (or cefotaxime if there is neonatal jaundice) should be combined with ampicillin which is added to cover Listeria monocytogenes infection. The length of the course of antibiotics given depends on the causative organism and the clinical progress of the patient. Beyond the neonatal period, dexamethasone administered with the antibiotics reduces the risk of long-term complications such as deafness. Any child who develops bacterial meningitis with an organism against which they have been immunised should be investigated for underlying immunodeficiency. .

Cerebral complications These include: Hearing loss. Inflammatory damage to the cochlear hair cells may lead  to deafness. All children who have had meningitis should have an audiological assessment promptly, as children who become deaf may benefit from hearing amplification or a cochlear implant. Local vasculitis. This may lead to cranial nerve palsies or other focal  lesions. Local cerebral infarction. This may result in focal or multifocal seizures  which may subsequently lead to epilepsy. Subdural effusion. Particularly associated with Haemophilus  influenzae and pneumococcal meningitis. This is confirmed by CT scan. Most resolve spontaneously. Hydrocephalus. May result from impaired resorption of CSF. A  ventricular shunt may be required. Cerebral abscess. The child's clinical condition deteriorates with the  emergence of signs of a space-occupying lesion. The temperature will continue to fluctuate. It is confirmed on CT scan. Drainage of the abscess is required

Prophylaxis

Prophylactic treatment with rifampicin 10MG per kg per day for 3 days or cefotriaxon sulpha or ciplox if > 12 yrs old age as alternative is given to PT and all household contacts for meningococcal meningitis and Household contacts of patients who have had group C meningococcal meningitis should be vaccinated with the meningococcal group C vaccine Rifampicin only given for PT and young children < 4 yrs in the household for Haemophilus influenzae infection. It is not required for the patient if he has received a third-generation cephalosporin as this will eradicate nasopharyngeal carriage.

Specific causes

Meningococcal infection In the UK, Neisseria meningitidis (meningococcus) is the most common cause of meningitis. The incidence increased in the late 1990s but since then has fallen markedly following the introduction of the conjugate vaccine against group C disease in 1999. In countries where it remains endemic, outbreaks may occur. Meningococcal infection is a disease that strikes fear into both parents and doctors as it can kill previously healthy children within hours. While meningitis is the main clinical form of infection with this organism, meningococcal septicaemia carries a worse prognosis . Of the three main causes of bacterial meningitis, meningococcal has the lowest risk of long-term neurological sequelae, with most survivors recovering fully. The septicaemia is accompanied by a purpuric rash which may start anywhere on the body and then spread. The rash may or may not be present with meningococcal meningitis. Characteristic lesions are (non-blanching on palpation, irregular in size and outline and have a necrotic centre ). Any febrile child who develops a purpuric rash should be treated immediately, at home or in the general practitioner's surgery, with systemic antibiotics such as penicillin before urgent admission to hospital. Although there are now polysaccharide conjugate vaccines against groups A and C

Classic Symptoms The first classic symptom was rash, which appeared at 8-9 hours (median time) in babies and young children, but later in older children. Although not always present, it was the most common classic feature of meningococcal disease. Meningitis symptoms (neck stiffness, photophobia, bulging fontanelle) appeared later – 12 to 15 hours from onset. They were more common in older children and were not reliable signs in children under age 5. Late features such as confusion/delirium/impaired consciousness eventually developed in nearly half of children, while seizures and coma were uncommon. They occurred 15 to 24 hours from disease onset .

NICE GUIDLINE FOR MANAGMENT OF MENEGIOCOCCAL INFECTION

Treatment and further action Antibiotic Therapy If meningococcal infection is suspected, the patient should be transferred to hospital by quickest means of transport, usually emergency ambulance, and parenteral antibiotics should be given at the earliest Opportunity usually while arranging transport to hospital. Urgent transfer to hospital is the key Priority. The evidence on effectiveness of pre-hospital antibiotics is inconclusive, because disease severity is a confounding factor recommendation advise giving parenteral antibiotics for suspected meningococcal disease at the prehospital stage. Antibiotics can be administered IV, IM, or IO. IM antibiotics should be given as proximally as possible, into a part of the limb that is still warm (the cold area being more poorly perfused). Choice of antibiotic: Pre-hospital administration of benzylpenicillin has been recommended since 1988 iF a history of immediate allergic reactions after previous penicillin administration. GPs do not need to carry alternative antibiotics, but third generation cephalosporins (cefotaxime rather than ceftriaxone for first line use in meningococcal septicaemia and chloramphenicol are recommended alternatives if available.

Supportive Treatment (if facilities are available) If a patient is unconscious, airways management should be implemented. Oxygen should be administered, particularly when the respiratory rate is raised, suggesting shock or pulmonary oedema. Rapid heart rate, poor capillary refill time and cold extremities suggest hypovolaemia and IV fluids should be administered to prevent circulatory collapse. This should not delay antibiotic therapy or transport to hospital . Transfer to Hospital The patient should be transferred to hospital by the quickest means of transport, usually 999 ambulance. Ambulance control and hospital staff need to know the diagnosis, whether the patient has a non-blanching rash, and especially whether there are serious prognostic signs such as a rapidly evolving rash, shock, or impaired conscious level. A GP referring a patient to hospital should contac the on-call paediatrician/emergency personnel so that they can expect this patient . Case Notification The doctor who suspects a diagnosis of meningitis or meningococcal septicaemia in the UK has a legal duty to notify the case to the local Consultant in Communicable Disease Control (CCDC) or Consultant in Public Health Medicine (CPHM) or the on-call Public Health Specialist. This is usually done by the hospital, but GPs may wish to check that it has been done. Dealing with Patient Contacts The CCDC or CPHM is responsible for ensuring that intimate and household contacts of a patient with meningococcal disease who require antibiotic prophylaxis are prescribed rifampicin, ciprofloxacin or ceftriaxone. This is restricted to those contacts identified by public health. The purpose of chemoprophylaxis is to eliminate carriage in the contact group, it does not prevent illness in those already incubating the bacteria, so contacts should continue to be alert to the possibility ofmeningococcal disease, and given a leaflet to help them recognise the symptoms

confirming the diagnosis

laboratory diagnosis

BLOOD CULTURE Blood culture has been the gold standard for the definitive diagnosis of IMD, and LP for meningitis should be collected as soon as possible after admission to hospital, but should not delay treatment. Blood polymerase chain reaction (PCR) for meningococcal DNA has high sensitivity (88%,) and specificity (100%) Lumbar puncture is not recommended in the initial assessment of suspected IMD with features of septicaemia. LP may be considered later if there is diagnostic uncertainty or unsatisfactory clinical progress, and there are no contraindications. lumbar puncture should be performed in patients with clinical meningitis without features of septicaemia (purpura) where there are no contraindications. cerebrospinal fluid should be submitted for microscopy, culture and pcr.

TREATMENT parenteral cefotaxime should be used as initial treatment of previously well children over three months with a diagnosis of IMD. ; Once daily ceftriaxone monotherapy may be substituted if calcium containing parenteral agents have not been used in the preceding 48 hours. ; When parenteral antibiotics are indicated for infants less than three months of age,cefotaxime plus an antibiotic active against listeria (eg ampicillin or amoxicillin) should be given. Current UK practice favours seven days‘ antibiotic therapy. in children beginning empirical antibiotic treatment for bacterial meningitis of unknown aetiology or meningiococcal or h influnza , parenteral dexamethasone therapy (0.15 mg/kg six hourly) should be commenced with, or within 24 hours of, the first antibiotic dose, and be continued for four days.

Follow up care for survivors Although most people recover well, there is a wide range of possible long term sequelae: ● hearing loss and other sensory disabilities ● neurological damage including learning, motor and neuro-developmental deficits and epilepsy ● orthopaedic damage including amputation, growth plate damage and arthritis ● post necrotic tissue/skin loss requiring reconstructive surgery ● renal impairment or chronic damage to other organ systems ● psychiatric and behavioural problems including post-traumatic stress disorder.

Patients who survive meningococcal disease require follow-up and need to be thoroughly assessed forany long-term complications. This should include hearing assessment : children should have their hearing tested as soon as possible, but within 4 weeks of being fit to test (post-meningitis ossification of the inner ear occurs rapidly and can prevent or limit successful cochlear implantation in those with profound hearing loss). Hearing tests may need to be repeated and may require referral from general practice. Psychological follow up is important as children may have difficulty readjusting after discharge,particularly those treated on PICU . Early referral to Child and Adolescent Mental Health Services may be necessary. Parents as well as children may be prone to post-traumatic stress disorder. In some cases, sequelae do not become evident until years after the illness, long after routine follow up has ceased: ● learning impairment and coordination difficulties are sometimes only noticed when children reach school age ● distorted bone growth due to growth plate damage may take years to become apparentIn such cases, children need referral from their GP for assessment and follow up care.

Haemophilus meningitis Before the introduction of Hib vaccine, H. influenzae type b was the second most common cause of meningitis in the UK and the most common in the USA. Immunisation has been highly effective and this is now a rare cause of meningitis. Pneumococcal meningitis While this organism was responsible for only 10% of meningitis before Hib vaccine was introduced, its prominence has now increased. Routine immunisation with the new protein-polysaccharide conjugate vaccine should reduce the high mortality (10%) and morbidity associated with this disease, as more than 30% of survivors develop neurological impairment. Partially treated bacterial meningitis Children are frequently given oral antibiotics for a non-specific febrile illness. If they have early meningitis, this partial treatment with antibiotics may cause diagnostic problems. CSF examination shows a raised number of white cells low glucose and high protein , but cultures are usually negative. Rapid antigen screen or PCR is sometimes helpful in these circumstances. Where the diagnosis is suspected clinically, a full course of antibiotics should be given

Tuberculous meningitis

Tuberculous meningitis is rare in the UK . The onset of the illness is often insidious, over 2-3 weeks. Meningism may be minimal. There may be a history of TB contact. Most, but not all, affected children have a positive Mantoux test and abnormal chest X-ray. The acid-fast bacilli may be identified on Ziehl-Nielsen or auramine staining of the CSF or in early morning urine samples or gastric aspirates. As there are few organisms, they are easily missed. PCR may aid diagnosis. The mycobacteria may take 2-3 months to culture, but ascertainment of the sensitivities of the organism is important as multidrug resistance is increasing. Treatment should be started empirically when the CSF shows the features suggestive of TB meningitis. The disease is associated with a high mortality and morbidity, especially when treatment is only started after reduced consciousness or when focal neurological signs are present. Four antituberculous drugs will be required for 2 months (e.g. rifampicin, pyrazinamide isoniazid and ethambutol), decreasing if the organism is fully sensitive to two drugs (isoniazidl " and rifampicin) to complete a total of at least one year of treatment. Dexamethasone should be given for the first month at least, to decrease the risk of long-term sequelae.

Viral meningitis

Overall, two-thirds of CNS infections are viral. Causes include enteroviruses, Epstein-Barr virus, adenoviruses and mumps. Mumps meningitis is now rare in the UK due to MMR vaccine. The illness is usually much less severe than bacterial meningitis and a full recovery can be anticipated.

Diagnosis of viral meningitis can be confirmed by culture or PCR of CSF; culture of stool, urine, nasopharyngeal aspirate, throat swabs; and serology

Encephalitis/Encephalopathy Whereas in meningitis there is inflammation of the meninges, in encephalitis there is inflammation of the brain substance, although the meninges are often also affected. Encephalitis may be caused by: direct invasion of the cerebrum by a neurotoxic virus (HSV)  delayed brain swelling following a disordered neuroimmunological response to  an antigen, usually a virus (post-infectious encephalopathy), e.g. following chickenpox slow virus infection, such as HIV infection or subacute sclerosing  panencephalitis (SSPE) following measles. In encephalopathy from a non-infectious cause, e.g. a metabolic abnormality, the clinical features may be similar to an infectious encephalitis. The clinical features and investigation of encephalitis are described in Most children present with fever, altered consciousness and often seizures. Initially, it is not possible to clinically differentiate encephalitis from meningitis, and treatment for both should be started. The underlying causative organism is only detected in up to 50%. In the UK, the most frequent causes of encephalitis are enteroviruses, respiratory viruses and herpesviruses (e.g. varicella and HHV6). Worldwide, microorganisms causing encephalitis include Mycoplasma, Borrelia burgdorferi (Lyme disease), Bartonella henselae (cat scratch disease), rickettsial infections (e.g. Rocky mountain spotted fever) and the arbovirusues.

Herpes simplex virus (HSVII)(10%) is a very rare cause of childhood encephalitis but it may have devastating long-term consequences. All children with encephalitis should therefore be treated initially with aciclovir to cover this possibility. Most affected children do not have outward signs of herpes infection, such as cold sores, gingivostomatitis or skin lesions. The PCR of the CSF may be positive for HSV. As HSV encephalitis is a destructive infection, the EEG and CT/MRI scan may show focal changes, particularly within the temporal lobes These tests may initially give non-specific results and require to be repeated after a few days if the child is not improving. Later confirmation of the diagnosis may be made from HSV antibody production in the CSF. Proven cases of HSV encephalitis or cases where there is a high index of suspicion should be treated with intravenous aciclovir for 3 weeks, as relapses have occurred after shorter courses of treatment. Untreated, the mortality rate from HSV encephalitis is over 70% and survivors usually have severe neurological sequela