ATAXIA-PG DISCUSSION

3 yr old child had hand foot mouth disease 1 wk ago , now presents with unstediness of gait. she can sit,but cannot hold spoon. there was no vomiting or fussiness. no h/o ingestion of medications. no h/o eardicharge/ uri

 

• What is the probable dx?
• What are the life threatening causes?
• What are the common causes?
• What all points in history are to be noted?
• What do you specifically look in physical examination?

 

Acute ataxia is an uncommon presenting complaint in children. Although causes of acute ataxia include life-threatening conditions such as mass lesions and central nervous system (CNS) infection, the majority of children have a benign, self-limited process. Historical features, specific physical findings, and selected ancillary studies can identify most causes of ataxia, particularly those that are serious and require stabilization and intervention

.

Acute cerebellar ataxia — Acute cerebellar ataxia is the most common cause of childhood ataxia, accounting for about 30 to 50 percent of all cases. It is a self-limited syndrome that is frequently postinfectious and typically seen in children between two and five years of age. The diagnosis of acute cerebellar ataxia can only be made after exclusion of other more serious illnesses such as toxic ingestions, central nervous system infection, structural intracranial lesions, metabolic derangement, or neurodegenerative disorders

Life-threatening conditions

•  Life-threatening causes of acute ataxia in children are fortunately uncommon. For those conditions that create a mass effect, signs and symptoms of increased intracranial pressure (such as vomiting, headache, or papilledema) are typically evident. Etiologies include tumors, hemorrhage, stroke, and infection

 

History —

•  Most children with ataxia present with refusal to walk or with a wide-based, “drunken” gait. Specific features of the history that may help to identify the underlying cause of the ataxia include the following:
• Onset of symptoms – A rapid onset is typically indicative of a traumatic, infectious, post-infectious, or toxic etiology. Guillain-Barré syndrome (GBS) and metabolic syndromes usually present with a slower, more progressive onset of symptoms, usually over a few days. A slower and relatively insidious course is characteristic of brainstem and cerebellar tumors, although medulloblastomas may grow rapidly, and acute decompensation may occur secondary to obstructive hydrocephalus or hemorrhage into the lesion.
• Associated symptoms – Important associated symptoms include:•Otalgia, vertigo, and vomiting in association with acute ataxia suggest acute labyrinthitis. An older child with inner ear disease may complain of dizziness. Most children also have nystagmus.
• Recurrent night-time or early-morning headaches with or without vomiting are symptoms of increased intracranial pressure that may develop with a brain tumor. The absence of these symptoms, however, does not exclude the diagnosis. Personality and behavioral changes may also signal the presence of increased intracranial pressure with hydrocephalus.
• Abnormal mental status is a worrisome symptom that can develop in many conditions that cause acute ataxia, including mass lesions, central nervous system (CNS) infection, toxic exposure, trauma, stroke, and inborn errors of metabolism.
• Access to medications (prescription medications, anticonvulsants, over-the-counter drugs, drugs of abuse, and ethanol), and other toxic substances should be determined.
• A history of antecedent head trauma is consistent with an intracranial injury, whereas neck trauma suggests a stroke as the result of a vascular injury to the vertebral or basilar artery.
• Patients with a recent infection or vaccination may have a post-infectious demyelinating process such as acute cerebellar ataxia, GBS, or acute post-infectious demyelinating encephalomyelitis (ADEM).
• Previous similar episodes of acute ataxia suggest an episodic disorder such as a migraine syndrome, seizure, or inborn error of metabolism.
• Children with family members with ataxia may have migraine syndromes, hereditary ataxias, or inborn errors of metabolism.

Physical examination —

•  A systematic, yet flexible, approach to the physical examination is necessary to localize the source of the child’s symptoms. For young children who may be anxious or uncomfortable, careful observation of the patient’s movements and social interactions with the caregiver may provide more information than some parts of the formal examination.

General examination —

•  Abnormal vital signs must be recognized immediately. As an example, bradycardia, abnormal respiratory pattern, and hypertension may occur with increased intracranial pressure. The presence of fever is consistent with an infectious process. Other pertinent features of the general examination include the following:
• Bulging of the anterior fontanel may indicate increased intracranial pressure with a life-threatening cause of ataxia.
• An ipsilateral head tilt may be associated with posterior fossa tumors.
• For the child who tolerates a funduscopic examination, papilledema indicates increased intracranial pressure as may occur in posterior fossa tumors that obstruct spinal fluid flow leading to hydrocephalus.
• Nystagmus can develop with vestibular, cerebellar, or brainstem disorders. Opsoclonus may be associated with an occult neuroblastoma.
• Otitis media and hearing loss in association with vomiting and intense vertigo indicate acute labyrinthitis.
• Meningismus with fever and a toxic appearance is concerning for a CNS infection.
• A healing rash or viral exanthem may be a clue to the infectious antecedent in acute post-infectious cerebellar ataxia. Tick paralysis may be the cause of ataxia when an attached tick is noted.

Neurologic examination — The neurologic examination includes specific examination techniques as well as observations made while taking the history and throughout the general physical examination. The approach to the neurologic examination of a child is discussed in detail separately.

Findings that are associated with various causes of acute ataxia include the following:

• Mental status – Abnormal mental status suggests ingestion, ADEM, meningitis, encephalitis, or stroke. Lethargy may be present in many inborn errors of metabolism. By comparison, children with post-infectious acute cerebellar ataxia are normally alert and interactive.
• Cranial nerves – Abnormalities of cranial nerve function suggest posterior fossa lesions, brainstem encephalitis, or the Miller Fisher syndrome.
• Motor examination – Children with the acute onset of weakness may stagger as an attempt to compensate. This gait abnormality may be mistaken for true ataxia and has been called “paretic” ataxia. Paretic ataxia is proportional to the degree of weakness. It may be due to Guillain-Barré syndrome (GBS), botulism, myasthenia gravis, transverse myelitis, or tick paralysis [10]. Deep tendon reflexes are absent in patients with GBS, botulism, and tick paralysis.
• Sensory examination – Impairment of proprioceptive input may result in sensory ataxia, as may occur with GBS.
• Cerebellar examination – A cerebellar lesion is the likely cause of ataxia for a patient with an abnormal cerebellar examination. However, patients with significant cerebellar dysfunction may have no specific findings. Cerebellar signs include abnormalities in gait, speech, and coordination of voluntary movement. Gait is typically wide-based, unsteady, lurching, or staggering. Speech abnormalities include fluctuations in clarity, rhythm, tone, and volume. Patients may have difficulty maintaining truncal position (titubation). Coordination of voluntary movement, as demonstrated with over- or under-shooting (best seen on finger-nose testing) and difficulty with rapid alternating movements (dysdiadochokinesia), is poor. Hypotonia and tremor may also occur.

Findings that localize the disorder within the cerebellum include the following:

• Vermis (midline cerebellar) lesions cause dysarthria, truncal titubation and gait abnormalities.
• Lesions of the cerebellar hemispheres result in ipsilateral limb dysmetria, hypotonia, and tremor. Children may veer in the direction of the affected cerebellar hemisphere when walking.

Laboratory

• Toxicologic screen – A urine screen for drugs of abuse or blood for specific drug levels (as suggested by the history) may be the most useful diagnostic test for children with acute ataxia if clinically suspected
• Blood glucose – A bedside test for blood glucose will quickly identify children with hypoglycemia.
• Metabolic evaluation – For children with episodic acute ataxia and other features that suggest an inborn error of metabolism (such as altered mental status or family history), the following tests may be useful: liver function tests, blood pH, CBC, quantitative amino acid determinations of blood and urine, serum lactate, pyruvate and ammonia levels, and urine organic acids.
• Cerebrospinal fluid (CSF) examination – CSF should be obtained whenever there is concern for CNS infection, such as meningitis or encephalitis. Otherwise, CSF examination is rarely indicated for the emergent evaluation of a child with acute ataxia. Moderate CSF protein elevation can occur in acute cerebellar ataxia, ADEM, and multiple sclerosis. CSF protein is also usually elevated in Guillain-Barré syndrome, but it may be normal in as many as 20 percent of children within a week of symptom onset [2]. Neuroimaging should be obtained before a lumbar puncture is performed when there is concern for increased intracranial pressure.
• Imaging — Neuroimaging should be obtained for patients with acute ataxia who have altered levels of consciousness, focal neurologic signs, cranial neuropathies, marked asymmetry of ataxia, concern for a mass lesion, or a history of trauma. Imaging may also be helpful when considering a diagnosis of exclusion, such as acute cerebellar ataxia or a conversion disorder.
• Magnetic resonance imaging (MRI) is the imaging modality of choice for patients with acute ataxia, although MRI may be difficult to obtain emergently. It is superior to computed tomography (CT) for detection of posterior fossa lesions such as tumors, strokes, and abscesses. In addition, patients with demyelinating diseases or brainstem encephalitis may have abnormalities detected with MRI.
• CT is generally more available emergently than MRI. CT can usually detect conditions that require immediate surgical intervention such as hydrocephalus, traumatic injury, and many mass lesions.
• Electrophysiologic studies — Electrophysiologic studies are rarely necessary for the evaluation of acute ataxia. In consultation with a pediatric neurologist, EEG is indicated for children who may be having seizures, as suggested by altered levels of consciousness and/or fluctuating clinical signs. EEG may also demonstrate nonspecific abnormalities that are clues to a metabolic etiology or toxic exposure. Although electrophysiologic studies are the most specific and sensitive tests for diagnosis of Guillain-Barré syndrome, they may not be helpful early in the disease

Which  all Congenital disease  can cause ataxia?

 

• Agenesis of vermis of the cerebellum
•  Aplasia or dysplasia of the cerebellum
•  Basilar impression
•  Cerebellar dysplasia with microgyria, macrogyria, or agyria
•  Cervical spinal bifida with herniation of the cerebellum (Chiari malformation type 3)
• Chiari malformation
•  Dandy–Walker syndrome
•  Encephalocele
•  Hydrocephalus (progressive)
•  Hypoplasia of the cerebellum

 Which all Degenerative and/or Genetic illness can cause ataxia?

 

 

• Acute intermittent cerebellar ataxia [Hill and Sherman*]
•  Ataxia, retinitis pigmentosa, deafness, vestibular abnormality,and intellectual deterioration [Francois and Descampas*]
•  Ataxia-telangiectasia
•  Biemond’s posterior column ataxia
•  Cerebellar ataxia with deafness, anosmia, absent caloric responses, nonreactive pupils, and hyporeflexia [Brown, 1959]
•  Cockayne’s syndrome
•  Dentate cerebellar ataxia (dyssynergia cerebellaris progressiva)
•  Familial ataxia with macular degeneration [Foster and Ingram*]
•  Friedreich’s ataxia
•  Hereditary cerebellar ataxia, intellectual retardation, choreoathetosis,and eunuchoidism [Altchule and Kotowski*]
• Hereditary cerebellar ataxia with myotonia and cataracts [Brown,1959]
•  Hypertrophic interstitial neuritis
•  Marie’s ataxia
•  Marinesco–Sjo¨ gren syndrome
•  Pelizaeus–Merzbacher disease
•  Periodic attacks of vertigo, diplopia, and ataxia – autosomaldominant inheritance [Farmer and Mustian*]
•  Posterior and lateral column difficulties, nystagmus, and muscle atrophy [Burge and Wuthrich*]
•  Progressive cerebellar ataxia and epilepsy [von Bogaert and Colle*]
•  Ramsay Hunt disease (myoclonic seizures and ataxia)
•  Roussy–Le´ vy disease
•  Spinocerebellar ataxia (SCA); olivopontocerebellar ataxias

 Which all Endocrinologic illness can cause ataxia?

• Acquired hypothyroidism
•  Cretinism

WHICH all Infectious or Postinfectious state can cause ataxia

• n Acute cerebellar ataxia
•  Acute disseminated encephalomyelitis
•  Cerebellar abscess
•  Coxsackievirus
•  Diphtheria
•  Echovirus
•  Fisher’s syndrome
•  Infectious mononucleosis (Epstein–Barr virus infection)
•  Infectious polyneuropathy
•  Japanese B encephalitis
•  Mumps encephalitis
•  Mycoplasma pneumonia
•  Pertussis
•  Polio
•  Postbacterial meningitis
•  Rubeola
•  Tuberculosis
•  Typhoid
•  Varicella

which all Metabolic disease can ataxia?

 

• Abetalipoproteinemia
•  Argininosuccinic aciduria
•  Ataxia with vitamin E deficiency (AVED)
•  GM2 gangliosidosis (late)
•  Hartnup’s disease
•  Hyperalaninemia n Hyperammonemia I and II
• Hypoglycemia
• Kearns–Sayre syndrome
• Leigh’s disease
• Maple syrup urine disease (intermittent)
• Myoclonic epilepsy with ragged red fibers (MERRF)
• Metachromatic leukodystrophy
• Mitochondrial complex defects (I, III, IV)
• Multiple carboxylase deficiency (biotinidase deficiency)
• Neuronal ceroid-lipofuscinosis
• Neuropathy, ataxia, retinitis pigmentosa (NARP)
• Niemann–Pick disease (late infantile)
• 5-Oxoprolinuria
• Pyruvate decarboxylase deficiency
• Refsum’s disease
• Sialidosis
• Triose-phosphate isomerase deficiency
• Tryptophanuria
• Wernicke’s encephalopathy

 

what are the Neoplastic illness that can cause ataxia?

 

• Frontal lobe tumors
• Hemispheric cerebellar tumors
• Midline cerebellar tumors
• Neuroblastoma
• Pontine tumors (primarily gliomas)
• Spinal cord tumors
• rimary Psychogenic
• Conversion reaction

which all Toxic substance can cause ataxia?

• Alcohol
• Benzodiazepines
• Carbamazepine
• Clonazepam
• Lead encephalopathy
• Neuroblastoma
• Phenobarbital
• Phenytoin
• Primidone
• Tic paralysis poisoning
• Raumatic
• Acute cerebellar edema
• Acute frontal lobe edema

which all vascular illness can cause ataxia?

• Angioblastoma of cerebellum
• Basilar migraine
• Cerebellar embolism
• Cerebellar hemorrhage
• Cerebellar thrombosis
• Posterior cerebellar artery disease Vasculitis
• von Hippel–Lindau disease

which are the treatable causes of ataxia?

 

Ataxia with vitamin E deficiency	Mutation in a-tocopherol transfer protein	Ataxia, areflexia, retinopathy	Vitamin E
Bassen–Kornzweig syndrome	Abetalipoproteinemiaj	Acanthocytosis, retinitis pigmentosa, fat malabsorption	Vitamin E
Hartnup’s disease	Tryptophan malabsorption	Pellagra rash, intermittent ataxia	Niacin
Familial episodic ataxia type 1 and type 2	Mutations in potassium channel (KCNA1) and a1A voltage-gated calcium channel, respectively	Episodic attacks, worse with pregnancy or birth control pills	Acetazolamide
Multiple carboxylase deficiency	Biotinidase deficiency	Alopecia, recurrent infections, variable organic aciduria	Biotin
Mitochondrial complex defects	Complexes I, III, IV	Encephalomyelopathy	Possibly riboflavin, CoQ10, dichloroacetate
Pyruvate dehydrogenase deficiency	Block in E-M and Krebs cycle interface	Lactic acidosis, ataxia	Ketogenic diet, possibly dichloroacetate
Refsum’s disease	Phytanic acid, a-hydroxylase	Retinitis pigmentosa, cardiomyopathy, hypertrophic neuropathy, ichthyosis	Dietary restriction of phytanic acid
Urea cycle defects	Urea cycle enzymes	Hyperammonemia	Protein restriction, arginine, benzoate, a-ketoacids

 

 

What is the anatomical basis of cerebellar signs?

 

. Midline Lesions

The middle zone of cerebellum consists of the vermis and flocculonodular lobe

and their associated subcortical nuclei.

These structures are involved in control of:

• Axial functions (eye movements) head and neck postures.
• Stance.
• Gait.

The midline cerebellar disease thus results in:

• Nystagmus and other disorder of ocular movements.( nystagmus and related ocular oscillations, gaze paresis, defective saccadic and pursuit movement)
• Instability of stance.
• Gait ataxia.

 

2. 2. Hemispheric Lesions

The lateral zones of cerebellum are represented by cerebellar hemispheres. They

are concerned with:

• Coordination of movements in the ipsilateral limb.
• Maintenance of tone in the ipsilateral limb.
• Regulation of ipsilateral gaze.

The disorder of those structures leads to:

• Ipsilateral hemiataxia.
• Ipsilateral hypotonia.
• Nystagmus.
• Transient ipsilateral gaze paresis (inability to look voluntarily towards the

side of affected hemisphere).

• Dysarthria (though traditionally considered a manifestation of midline cerebellar disease, dysarthria correlates more closely with paramedian lesions in the left cerebellar hemisphere

how to assess cerebellar signs in a child?

 

• Testing coordination, for example, is not even part of the newborn neurological examination. Cerebellar assessment awaits the acquisition offine motor skills. As the baby acquires a pincer grasp and begins to manipulate small objects,fine motor testing assumes the characteristics of coordination testing.
• Maturing of the cerebellarsystem can be seen as the infant progresses from sitting without support to cruising (taking stepswith a wide-based or toddler’s gait.
• At 3 years ofage, the child is able to balance on one foot, and at 4 years the child can hop on one foot. By6 years of age most children can narrow their station (stance) to the point of being able totandem walk and maintain sufficient balance to ride a bicycle. Thus, cerebellar testing must takeinto account the developmental level of the child and the acquisition of normal milestones.Ataxia can be thought of in terms of two main categories: gait and truncal ataxia or appendicular (extremity) ataxia. Stability of the trunk and coordination in walking is predominantly a function of the midlinestructures of the cerebellum (the vestibulo – cerebellum and spinocerebellum).
• By contrast,fine motor coordination of the extremities is the function of the cerebellar hemispheres(neocerebellum). Testing of cerebellar func – tion is usually directed toward assessment of the extremities and then assessment of trunk stability and gait coordination. The standard tests for appendicular coordination include repetitive finger and foot tapping, front-toback hand patting (20) (diadochokinesia), finger-to-nose and heel-to-shin testing.
• Trunk and gait assessment is accomplished by observing the child get in and out of a sitting position, noting stability in the sitting and standing positions, and watching the child walk and performing age-appropriate skills such as hopping, walking tandem, or balancing on one foot. For the older child, the standard coordina – tion examination can be used, but adaptation is needed for the infant and toddler. The key is to

engage the child in playful activities that will interrogate coordination.

• For example, pickingup a small object such as a small wad of papercan be used for testing extremity fine motor coordination (21). The child can reach for andgrasp the examiner’s reflex hammer or the end of the measuring tape (22). For finger-to-nosetesting, ask the child to touch the nose or eyes of a finger puppet and then to touch their ownnose (23). Older children and adolescents can perform standard finger-to-nose testing(24–28). Using blocks or other stacking toys is another useful assessment strategy. Because theunder- and over-shooting movement of ataxia resembles a tremor, this type of ataxia is oftencalled an intention or ataxic tremor. This tremor is greatest at the end point or the mostdemanding part of the movement

 

 

what are the causes of acute or recurrent ataxia

 

Brain tumor

Conversion reaction*

Drug ingestion

Encephalitis (brainstem)

Genetic disorders

Dominant recurrent ataxia

Episodic ataxia type 1

Episodic ataxia type 2

Hartnup disease

Maple syrup urine disease

Pyruvate dehydrogenase deficiency

Migraine

Basilar

Benign paroxysmal vertigo*

Postinfectious/immune

Acute postinfectious cerebellitis

Miller Fisher syndrome*

Multiple sclerosis*

Myoclonic encephalopathy and neuroblastoma*

Progressive cavitating leukoencephalopathy

Pseudoataxia (epileptic)

Trauma

Hematoma*

Postconcussion*

Vertebrobasilar occlusion*

Vascular disorders

Cerebellar hemorrhage*

Kawasaki disease*

What are the causes of chronic ataxia?

 

Brain Tumors

Cerebellar astrocytoma*

Cerebellar hemangioblastoma* (Von Hippel-Lindau disease)

Ependymoma*

Medulloblastoma*

Supratentorial tumors*

Congenital Malformations

Basilar impression

Cerebellar aplasias

Cerebellar hemisphere aplasia

Chiari malformation*

Dandy-Walker malformation

Vermal aplasia

Hereditary Ataxias

Autosomal dominant inheritance

Autosomal recessive inheritance

Abetalipoproteinemia

Ataxia-telangiectasia

Ataxia without oculomor apraxia

Ataxia with episodic dystonia

Friedreich ataxia

Hartnup disease

Juvenile GM2 gangliosidosis

Juvenile sulfatide lipidoses

Maple syrup urine disease

Marinesco-Sjögren syndrome

Pyruvate dehydrogenase deficiency

Ramsay Hunt syndrome

Refsum disease (HSMN IV)

Respiratory chain disorders

X-Linked Inheritance

Adrenoleukodystrophy

Leber optic neuropathy With adult-onset dementia

With deafness

With deafness and loss of vision

 

What ia acute cerebellar ataxia?

 

• Acute cerebellar ataxia usually affects children between 2 and 7 years of age, but it may occur as late as 16 years. The disorder affects both genders equally, and the incidence among family members is not increased. In the past, acute cerebellar ataxia occurred most often following aricella infection. The widespread use of varicella vaccinehas made the syndrome uncommon. However, itis a complication of live-inactivated vaccine administration.

 

What are the clinical features of acute cerebellar ataxia?

 

Clinical Features.

• The onset is explosive. A previously healthy child awakens from a nap and cannot stand. Ataxia is maximal at onset. Some worsening may occur during the first hours, but a longer progression, or a waxing and waning course, negates the diagnosis. Ataxia varies frommild unsteadiness while walking to complete inability to stand or walk. Even when ataxia is severe, sensorium is clear and the child is otherwisenormal. Tendon reflexes may be present or absent; their absence suggests the Miller Fishersyndrome. Nystagmus, when present, is usually mild. Chaotic movements of the eyes (opsoclonus)should suggest the myoclonic encephalopathy-neuroblastoma syndrome. Symptoms begin to remit after a few days, butrecovery of normal gait takes 3 weeks to 5 months.Patients with pure ataxia of the trunk or limbs and only mild nystagmus are likely to recover completely.
•  Marked nystagmus or opsoclonus, tremors of the head and trunk, or moderate irritabilityare usually followed by persistent neurological sequelae.

How to dx acute cerebellar ataxia ?

 

• Diagnosis. The diagnosis of acute postinfectiouscerebellitis is one of exclusion. Every child should have drug screening, and most will havea brain imaging study. The necessity of imaging the brain in typical cases, especially those withvaricella infection, is debatable. Lumbar punctureis indicated when encephalitis is suspected.Management. Acute postinfectious cerebellitisis a self-limited disease. Treatment is not required. Occupational therapy may facilitateactivities during the recovery phase

 

 

 

 

what is ataxia telangiectasia?

• Ataxia-telangiectasia (AT) is one of the most common inherited causes of early childhood-onset ataxia in most countries, with a prevalence of 1 in 40,000–100,000 live births in the United States. The disease is characterized by progressivecerebellar ataxia, ocular apraxia, oculocutaneous telangiectasias, choreoathetosis, proclivity to sinopulmonary infections,and lymphoreticular neoplasia. Death often occurs bythe fourth or fifth decade of life, typically resulting from sinopulmonary disease, neoplasms, or from neurologicdeterioration.

CLINICAL MANIFESTATIONS

• Early motor development appears to be normal until around the time that the child starts walking, when ataxia is noted.The ataxia is progressive and ultimately leads to an inabilityto ambulate by the beginning of the second decade. Choreoathetosisand dystonia occur in up to 90 percent of patients, and these motor findings become more prominent withincreasing age. Facial weakness leads to the characteristic impassivefaces, as well as drooling and dysarthria. Mental function is well preserved,although deficits in short-term memory can occur in the third and fourth decades].
• Oculomotor apraxia is a distinguishing feature of the disease.The apraxia commonly presents before the appearance of conjunctival telangiectasias and is characterized by defectsof initiating voluntary saccades, hypometric voluntary saccadesaccompanied by compensatory eye-blinking and/or headthrustingmovements, and disrupted smooth pursuit movements Involuntarysaccade initiation and optokinetic nystagmus may be impairedas well, and oculovestibular reflexes may be increased.
• Telangiectasias are usually first observed in patients betweenthe ages of 2 and 4 years, although they can occur as early as birth and as late as 14 years of age  In addition to theconjunctivae, they appear on exposed areas of the skin,particularlyareas of friction and trauma, such as the auricle, nasal bridge, and antecubital and popliteal spaces. Exposure to sunenhances their appearance. Premature aging of hair and skinis frequent, as are skin infections, including chronic blepharitis.
• Other skin changes, consisting of vitiligo and cafe´-au-lait spots,can be seen. Rarely, scleroderma-like lesions occur.Recurrent sinopulmonary infections are common, affecting 90 percent of patients, and usually result in chronic bronchitis,bronchiectasis, or both. The impairment of cellularimmunity is also manifest by abnormally developed or absent adenoids, tonsils, lymphoid tissue, and thymus gland. Patientshave an impaired delayed hypersensitivity response toskin-sensitizing antigens and a delayed homograft-rejection response
• Patients with AT are prone to develop tumors and are morelikely than the general population to have Hodgkin’s disease, leukemia, lymphoma, and lymphosarcoma. Other associatedneoplasms include brain tumors, gastric adenocarcinomas,ovarian  dysgerminomas, gonadoblastomas, cystic adenofibromas,uterine leiomyomas, and thyroid adenomas.Hypogonadism is frequent in both genders, and growthretardation is notable’ despite normal levels of growth hormone.Insulin-resistant diabetes is also occasionally seen as part of the clinical constellation.Patients with less severe variant forms of AT have been described
• Immunodeficiency,telangiectasias, cancer, and sinopulmonary infectionsmay be absent or reduced, but the neurological manifestations still occur. These individuals have a later onset and slowerprogression of neurological signs, longer life spans, anddecreased chromosomal instability and cellular radiosensitivity

 

What is medulloblastoma?

 

• Medulloblastoma is a primitive neuroectodermal tumor (PNET) of the posterior fossa with the capacity to differentiate into neuronal and glialtissue. Most tumors are in the vermis or fourth ventricle, with or without extension into the cerebellarhemispheres. Approximately 10 % are in the hemisphere alone. Medulloblastomas represent approximately 85 % of intracranial PNETs and 15 % of all pediatric brain tumors. Datafrom the National Cancer Institute’s Surveillance, Epidemiology, and End Results (SEER)registry indicates an increasing incidence of medulloblastoma

What are the Clinical Features.?

• Ninety percent of cases have their onset during the first decade and theremainder during the second decade. Medulloblastomais the most common primary brain tumor with onset during infancy.The tumor grows rapidly, and the interval between onset of symptoms and medical consultationis generally brief: 2 weeks in 25 % of casesand less than a month in 50 %.
• Vomiting is an initial symptom in 58 % of children, headache in40 %, an unsteady gait in 20 %, and torticollis or stiff neck in 10 %. The probable cause of prominent vomiting, with or without headache, as an early symptom is tumor irritation of the floor ofthe fourth ventricle. Gait disturbances are more common in young children and refusal to standor walk is characteristic rather than by ataxia. Two-thirds of children have papilledema at thetime of initial examination. Truncal ataxia and limb ataxia are equally common, and both may bepresent. Only 22 % of children have nystagmus.Tendon reflexes are hyperactive when hydrocephalusis present and hypoactive when the tumor iscausing primarily cerebellar dysfunction.

Diagnosis.

• CT or MRI easily identifies medulloblastoma. The tumors are vascular and become enhanced when contrast mediumis used.

 

Management.

• The combined use of surgical extirpation, radiation therapy, and chemotherapy greatly improves the prognosis for children with medulloblastoma. The role of surgery is to provide histological identification, debulkthe tumor, and relieve obstruction of the fourth ventricle. Ventriculoperitoneal shunting reduces intracranial pressure even before decompressiveresection.
• The treatment of children less than 3 years of age at diagnosis is with chemotherapy alone or chemotherapy with field radiotherapy. The overall 5-year survival rate is approximately40 %. Survival is better (60–70 %) in children whohave gross total tumor resection compared withpartial resection or biopsy.
•  Craniospinal radiation increases survival better than local field radiation.The use of adjuvant chemotherapy significantly improves survival. Most initial recurrences occur at the primary site. One histological variant, anaplasticlarge cell medulloblastoma, carries a poorerprognosis because of a higher risk for early metastatic involvement and recurrence). The presence of dissemination is the single most important factor that correlates with outcome

what is the role of metabolic screening?

 

Blood

Abetalipoproteinemia     =Lipoproteins, cholesterol

Adrenoleukodystrophy     = Very-long-chain fatty acids

Ataxia-telangiectasia –       =IgA, IgE, α-fetoprotein

Hypobetalipoproteinemia =Lipoproteins, cholesterol

Mitochondrial disorders   = Lactate, glucose-lactate tolerance

Sulfatide lipidoses              =Arylsulfatase A

Urine

Hartnup disease                                 = Amino acids

Maple syrup urine disease*             = Amino acids

Fibroblasts

Carnitine acetyltransferase deficiency* =Carnitine acetyltransferase

GM2 gangliosidosis                           =    Hexosaminidase

Refsum disease                                 =  Phytanic acid

Bone Marrow                                    =   neurovisceral storage Sea-blue histiocytes

 

What is frederich ataxia?

 

• Friedreich Ataxia. Friedreich ataxia is the most common recessively inherited ataxia. The cause is an unstable triplet repeat of the frataxin geneon chromosome 9q13 (Bidichandani et al, 2012).The size at which the expansion causes disease is not established.

 

Clinical Features.

• The onset is usually between 2 and 16 years of age, but symptoms may begin later. The initial feature is ataxia orclumsiness of gait in 95 % of cases and scoliosis in 5 %. The ataxia is slowly progressive andassociated with dysarthria, depressed tendon reflexes, extensor plantar responses, foreshorteningof the foot creating a high arch, and loss of position and vibration senses. Two-thirdsof patients have a hypertrophic cardiomyopathy and 10 % have diabetes mellitus. An atypicalpresentation occurs in 25 %. These atypical syndromes include any of the following features:(1) onset after age 25 years; (2) present tendon reflexes; and (3) spastic paraparesis withoutataxia.

 

Diagnosis.

• The clinical features suggest the diagnosis and molecular genetic testing provides confirmation. Motor nerve conduction velocities in the arms and legs are slightly slower than normal. In contrast, sensory action potential sare absent or markedly reduced in amplitude. Spinal somatosensory evoked responses areusually absent. Common changes on the electrocardiogram (ECG) are reduced amplitude of T waves and left or right ventricular hypertrophy. Arrhythmias and conduction defects are uncommon.Management. The underlying disturbance is not curable, but symptomatic treatment is available. Surgical stabilization prevents severe scoliosis. Regular ECG and chest radiographs to determine heart size are useful to monitor the development of cardiomyopathy. Chestpain on exertion responds to propranolol, and congestive heart failure responds to digitalis. Patients with diabetes require insulin Treatment

 

What is episodic ataxia?

 

Episodic Ataxia Type 1 (Paroxysmal Ataxia and Myokymia)

• EA-1 results from a mutation of the potassium channel gene KCNA1 on chromosome 12p. The additional feature of continuous motor unitactivity (see Chapter 8) suggests a defect in membrane stability affecting the central andperipheral nervous systems.

Clinical Features.

• The onset of attacks is usuallybetween 5 and 7 years of age. Abrupt postural change, startle, exercise, and stress mayprovoke an attack. The child becomes aware of attack onset by the sensation of spreading limpness or stiffness lasting for a few seconds Incoordination, trembling of the head or limbs,and blurry vision often follow. Some children feel warm and perspire. Some can continuestanding or walking, but most sit down. Attacksusually last for less than 10 minutes but can be aslong as 6 hours. Myokymia of the face and limbsbegins at about age 12 years. Physical findingsinclude large calves, normal muscle strength, and widespread myokymia of face, hands, arms, andlegs, with a hand posture resembling carpopedalspasm. Electromyography (EMG) at rest shows continuous spontaneous activity (De Vries et al,2009)

Diagnosis.

• The basis for clinical diagnosis is the history of typical attacks and the family history.EMG confirms the diagnosis by showing continuous motor unit activity, most often in the hands but also in the proximal arm muscles and sometimes in the face.

Management.

• Some patients respond to daily antiepileptic drugs. When these fail, a trial of daily acetazolamide is reasonable

 

what is hartnup disease?

 

Hartnup Disease

• Hartnup disease is a rare disorder transmitted by autosomal recessive inheritance. The abnormal gene localizes to chromosome 5p15 (Nozaki et al, 2001). The basic error is a defect of amino acid transport in kidney and small intestine. The result is aminoaciduria and the retention ofamino acids in the small intestine. Tryptophan conversion is to nonessential indole productsinstead of nicotinamide.

Clinical Features.

• Affected children are normal at birth but may be slow in attaining developmental milestones. Most achieve only borderline intelligence; others are normal. Affected individualsare photosensitive and have a severepellagra-like skin rash after exposure to sunlight.Nicotinamide deficiency causes the rash. Many patients have episodes of limb ataxia, sometimesassociated with nystagmus. Mental changes, rangingfrom emotional instability to delirium or states of decreased consciousness, may occur.
• Examination reveals hypotonia and normal or exaggeratedtendon reflexes. Stress or intercurrent infection triggers the neurological disturbances, which maybe due to the intestinal absorption of toxic aminoacid breakdown products. Most patients have both rash and neurological disturbances, but eachcan occur without the other. Symptoms progressover several days and last for a week to a month before recovery occurs.
• Diagnosis. The constant feature of Hartnup disease is aminoaciduria involving neutral monoaminomonocarboxylicamino acids. These includealanine, serine, threonine, asparagine, glutamine, valine, leucine, isoleucine, phenylalanine, tyrosine, tryptophan, histidine, and citrulline.
• Management. Daily oral administration of nicotinamide, 50–300 mg, may reverse the skin and neurological complications. A high-protein diet helps make up for the amino acid loss and the disease is rare in populations with a superadequate diet.

 

What is miller fischer syndrome ?

 

Miller Fisher Syndrome

• Ataxia, ophthalmoplegia, and areflexia characterize the Miller Fisher syndrome. A similar disorderwith ataxia and areflexia but without k ophthalmoplegia is acute ataxic neuropathy. Somebelieve that Miller Fisher syndrome is a variant ofGuillain-Barré syndrome; others believe that it is a form of brainstem encephalitis. In support of the hypothesis of a Guillain-Barré-like, immune mediated hypothesis is the finding that Campylobacter jejuni serotype O:19 is a causative agent inboth Miller Fisher syndrome and Guillain-Barré syndromes (Ja

what is basilar migrane?

 

• The term basilar (artery) migraine characterizes recurrent attacks of brainstem or cerebellar dysfunctionthat occur as symptoms of a migraine attack. Children who experience basilar arterymigraine have typical migraine with aura at other times. Girls are moreoften affected than are boys. The peak incidence is during adolescence, but attacks may occur atany age. Infant-onset cases are more likely to present as benign paroxysmal vertigo.

 

 

C linical Features.

• Gait ataxia occurs in approximately 50 % of patients. Other symptomsinclude visual loss, vertigo, tinnitus, alternating hemiparesis, and paresthesias of the fingers, toes, and corners of the mouth. An abrupt loss of consciousnessmay occur, usually lasting for only a few minutes. Cardiac arrhythmia and brainstemstroke are rare life-threatening complications. A severe, throbbing, occipital headache usually followsthe neurological disturbances. Nausea and vomiting occur in less than one-third of cases.Children may have repeated basilar migraine attacks, but, with time, the episodes evolve into apattern of classic migraine. Even during attacksof classic migraine, the patient may continue to complain of vertigo and even ataxia

Diagnosis.

• EEG distinguishes basilar migrainefrom benign occipital epilepsy. The EEG shows occipital intermittent delta activity during and just after an attack in basilar migraine and occipitalsharp and spike and wave discharges in epilepsy.
• Management. Treatment of basilar arterymigraine is the same as for other forms of migraine . Frequent attacks require a prophylacticagent

 What is bppv?

• Benign paroxysmal vertigo is primarily a disorder of infants and preschool children but mayoccur in older children.

Clinical Features.

• Recurrent attacks of vertigo are characteristic. Vertigo is maximal at onset. True cerebellar ataxia is not present, but vertigois so profound that standing is impossible. The child either lies motionless on the floor or wants holding. Consciousness maintains throughout the event and headache is not associated.The predominant symptoms are pallor, nystagmus, and fright. Episodes last only for minutesand may recur at irregular intervals. With time, attacks decrease in frequency and stop completelyor evolve into more typical migraines. Migraine develops in 21 % (Lindskog et al, 1999).

Diagnosis.

• The diagnosis is primarily clinical,and laboratory tests are useful only to exclude other possibilities. A family history of migraine,though not necessarily paroxysmal vertigo, is positive in 40 % of cases. Some parents indicate that they experience vertigo with their attacks of migraine. Only in rare cases does a parent have a history of benign paroxysmal vertigo.
• Management. The attacks are so brief and harmless that treatment is not required. Migraine prophylaxis may be considered when the attacks are frequent.