Neurology

Question 1

2008 A Q1

Cerebral palsy is defined as a disorder of posture and movement due to an insult to the developing brain. What is the most common period for the responsible brain insult to occur?

A. Antenatal.
B. Intrapartum.
C. Neonatal.
D. 1 to 12 months.
E. After 12 months.

Answer 1

A. Antenatal.

Question 2

What are the classic clinical features of infant botulism?

Answer 2

• Constipation
• cranial nerve abnormalities
• hypotonia
• hyporeflexia
• respiratory difficulties

other signs and symptoms

• poor feeding
• weak cry
• irritability
• lethary/decreased activity

Question 3

What direction is the progressive weakness in infant botulism?

Answer 3

Descending.

Often starts with constipation several weeks prior to further symptom onset. Weakness then progresses over days.

Symptoms begin with cranial nerve involvement, loss of head control, weak cry, poor suck, impaired gag reflex, pooling of secretions and decreased oral intake.

Question 4

What is the treatment of infant botulism and what should be avoided?

Answer 4

Treatment is supportive and should be commenced prior to confirmation of diagnosis. Diagnosis can take several days and the disease can progress within hours.

Respiratory and nutritional care should be commenced.

Avoid neuromuscular blocking drugs and aminoglycosides (gentamicin, tobramicin). Aminoglycosides kill the botulism and release further toxin.

Question 5

What is the pathophysiology of infant botulism?

Answer 5

The anaerobic bacillus Clostrium botulin is ingested from either soil or honey. It colonises in the GI tract and produces a toxin absorbed by the terminal ileum.

Toxin binds to the presynaptic sides of the peripheral cholinergic synapses at ganglia and NMJs. Binding is irreversible and resolution of symptoms occurs when a new presynaptic terminal and synapse are sprouted. This takes approximately 6 months.

Question 6

This patient also has recurrent sprained ankles and cramping in her hands.

What is the diagnosis?

What are other key clinical features of this disease?

Answer 6

Charcot-Marie-Tooth disease is a demyelinating disorder of peripheral nerves. CMT1 is most common (40%) caused by duplication of PMP22 gene.

• Frequent sprained ankles caused by distal muscle weakness
• Loss of reflexes
• Pes cavus foot
• Hammer toes
• Distal calf muscle atrophy causing “stork leg” deformity.
• Clumsy walking due to motor and sensory loss
• Sensory loss gradual and mainly proprioception and vibration

Specific therapy not yet available, management is supportive.

Question 7

Describe Guillain-Barré syndrome.

Answer 7

Guillan-Barr

• Most common cause of acute flaccid paralysis in infants and children.
• Group of disorders
• 2/3 have antecedant respiratory of GI infection.
• Campylobacter is most common pathogen.
• Neurologic symptoms occur 2-4 post an what appears to be benign infection.

Predominant symptoms = pain and gait difficulty.

Lower extremity symmetric weakness may ascend over hours to day to involve arms and muscles of respiration.

If cranial nerve involvement, usually CNVII.

Physical examination shows symmetric weakness with diminished or absent reflexes.

Nadir or function at 2-4 weeks, with return of function occuring slowly over weaks to months.

Diagnosis

• LP after 1 week of symptoms - Normal pressure, <10 cells with raised protein (>45gm/dL)
• MRI with contrast - enhancement of spinal nerve roots and cauda equina.
• Nerve conduction studies

Question 8

What is the cardinal feature of myasthenia gravis?

Answer 8

Fluctuating skeletal muscle weakness, often with true muscle fatigue.

Question 9

Myasthenia Gravis clinical features

Answer 9

Autoimmune disorder of neuromuscular transmission. Autoantibodies attack acetylcholine receptor (AChR), fix complement and decrease number of AChRs over time.

Uncommon - 10-20 new cases per million.

Bimodal ages of onset, peaks at 2nd-3rd decade (female predominance) and 6-8th decade (male predom)

Clinical features

Cardinal - fluctuating skeletal muscle weakness, often with true muscle fatigue (fatigue is worsening contractile force, not sensation of tiredness)

Weakness fluctuates throughout the day, usually worse evening/night or after exercise.

Look for:

• ocular - ptosis, eyelid fatigue, oculomotor paresis. Often unilateral or asymmetric. Historical alternating from side to side nearly always ocular myasthenia gravis.
  
  • No pupil abnormalities.
• Bulbar - Fatiguable chewing, dysarthria, dysphagia
• Facial - appears expressionless, lost smile/horizontal smile
• Weakened neck and proximal muscles
• Respiratory muscle weakness may lead to myasthenia crisis.

Question 10

Myasthenia Gravis diagnosis

Answer 10

1. Acetylcholine receptor antibodies
2. MuSK antibodies
3. Repetitive nerve stimulation
4. Single fibre electromyography

Question 11

Duchenne and Becker Muscular Dystophies

Pathogenesis and Clinical Features

Answer 11

X-linked recessive.

Caused by mutations of the dystrophin gene on X chromosome (usually deletions)

Principipal symptom is weakness due to muscle fibre degeneration.

Pathogenesis - Dystrophin provides mechanical reinforcement to the sarcolemma and stabilises the glycoprotein complex, shielding it from degradation. Without dystophin, the glycoprotein complex is digested by proteases. This initiates degeneration of muscle fibres resulting in weakness.

DMD

1.3-1.8 per 10,000

Weakness

• onset of weakness at 2-3 years, proximal before distal, lower before upper limbs.
  
  • difficulty running, walking, steps
  • Gower’s sign (using hand to get up from floor)
• Often wheelchair bound by age 12

Cardiac

• Primary dilated cardiomyopathy and conduction abnormalities

Orthopaedic

• Arm and leg #s frequent
• Scoliosis

Examination Findings

• Pseudohypertrophy of calf and quads
• lumbar lordosis
• waddling gait
• shortening of achilles
• hyporeflexia or areflexia

Becker Muscular Dystrophy

Cf DMD, age of onset of symptoms later and less severe.

Mental retardation and contractures less severe.

Often remain ambulatory until age 15 years and often into adult life.

Prognosis

Pts with DMD often confined to wheelchair by age 12 yrs and die in late teens or twenties from resp insufficiency or cardiomyopathy.

BMD usually survive beyond 30 years.

Question 12

Lab and Path findings in Duchenne and Becker muscular dystrophies

Answer 12

• Elevated CK (10-20 x upper limit of normal)
• ECG abnormalities
  
  • tall right precordial R waves with increased R/S ratio
  • deep Q waves in leads I, aVL, and V5-6
  • Supraventricular arrhthmias in DMD
• EMG - myopathic changes
• Muscle biopsy - degeneration, regeneration, hypertrophic fibres, significant replacement of muscle by fat and connective tissue
• Dystrophin analysis - almost complete absence

Question 13

Spinal muscle atrophy

Answer 13

An autosomal recessive group of disorders (types 1-4) characterised by degeneration of anterior horn cells in the spinal cord and motor nuclei in the lower brainstem.

SMA type 1 (infantile) is most common and most severe.

Presents in neonatal period, progresses quickly and most die before age 12 months from resp failure.

SMA 2 present b/w 3 and 15 months

SMA 3 (least severe) presents after one year

SMA 4 is adult onset, similar to SMA3. Presents 2nd-3rd decade.

Manifestations

• Diffuse proximal muscle weakness worse in lower limbs than upper.
• Absent or markedly decreased deep tendon reflexes
• SMA1 - severe symmetric flaccid paralysis, unable to sit unsupported
• Arthrogryposis (multiple joint contractures) may be present if prenatal onset
• Typically alert expression, normal eye movements
• Weakness of bulbar muscles = pooling of secretions, weak cry, poor suck and swallow, aspiration, tongue fasciculations
• Restrictive, progressive respiratory insufficiency

Diagnosis by muscle biopsy

Question 14

What is Rett syndrome?

Answer 14

A neurodevelopmental disorder that occurs almost exclusively in females.

• epilepsy
• regression of development
• hand wringing
• ataxic, broad based gait
• sudden cardiac death

Development is normally initially.

At 12-18 months there is lost of acquired fine motor, intellectual and communicative skills.

Regression can be rapid, or slowly progressing.

There are stereotypical hand movements which are incessant when awake, but cease during sleep (rubbing, clapping, kneading, pill rolling, hand opposition etc)

Broad based, ataxic, clumsy gait. Sometimes difficulty crossing from one type/colour floor surface to another.

Scoliosis in 50-85%

Question 15

Which anticonvulsant requires close serial measurements of serum levels due to narrow therapeautic index?

Answer 15

phenytoin

Question 16

In the hand, what do the ulnar, median and radial nerves supply?

Answer 16

Ulnar N -

• motor - intrinsic muscles of hand
• sensation - lateral fingers to lateral half of ring finger

Median N -

• motor - thumb adductors
• sensation - pointer and middle fingers to half of ring finger

Radial

• nil motor
• sensation - posterior thumb web

Question 17

Transverse myelitis

Answer 17

Transverse myelitis is characterised by rapid development of motor and sensory deficits.

Presents with discomfort/pain at the level of the lesion and progresses to numbness and weakness in the truncal and appendicular musculature.

Paralysis begins as flaccidity and over several weeks spasticity develops.

Urinary retention is an early finding with incontinence occurring later in the course.

Diagnosis made on the basis of clinical findings (bilateral sensorimotor and autonomic spinal cord dysfunction, clearly defined sensory level, progression to nadir of clinical deficits between 4h and 21 days after onset of symptoms), demonstration of spinal cord inflammation (CSF pleocytosis or MRI with gadolinium enhancing cord lesion) and exclusion of compressive, post-radiation, neoplastic and vascular causes.

Recovery is likely to be complete in older children but in younger children (<3 years), neurological recovery is often incomplete with only 40% likelihood of independent ambulation.


Question 18

What is the cellular action of botulinum neurotoxin?

Answer 18

Binding – toxin attaches rapidly and avidly to the presynaptic nerve membrane

Internalisation – toxin crosses the presynaptic membrane without causing onset of paralysis

Inhibition – toxin inhibits the release of acetylcholine, diminishing the endplate potential and causing impaired neuromuscular and autonomic transmission

Recovery of impulse transmission occurs gradually as new nerve terminals sprout and contact is made with the post-synpatic motor endplate (takes 6- 8 weeks)

Question 19

A 5 month old boy with congenital heart disease is evaluated because of motor delay.

Diagnosis?

Answer 19

Arachnoid Cyst
CT Scan demonstrates a large fluid collection in the left parietal-temporal region. The fluid is the same density as CSF. This scan and history is most consistent with an arachnoid cyst.
The brain tissue looks relatively normal which would make cerebral malformation less likely.
Blood is of a higher density than CSF (acute blood is white, chronic looks slightly darker than brain tissue)

Question 20

Anterior Horn cell disease is a form of SMA. How does it often present?

Answer 20

Because anterior horn cell disease affects the nerve cells responsible for body movements, precursors to the disease include severe reduced muscle tone, diminished limb movements, lack of muscle reflexes, body tremors, difficulty eating and drinking, breathing problems, or inability to stand.

Look for tongue fasciculations

Question 21

What side-effects are common to most antiepileptic medications?

Answer 21

Drowsiness, ataxia, tremor, nystagmus, dysarthria, confusion, nusea, vomiting, sleepiness or insomnia, mood disturbance.

Question 22

What are the idiosyncratic side effects of carbamazapine?

Answer 22

• rash
• leukopenia
• hyponatremia
• irritability
• weight gain

Question 23

What are the idiosyncratic SEs of lamotragine?

Answer 23

• Rash
• severe hypersensitivity syndrome

Question 24

What are the idiosyncratic SE’s of phenytoin?

Answer 24

• Rash
• Serum sickness type illness
• Extravasation

Question 25

What are the idiosyncratic SEs of Sodium Valproate?

Answer 25

• Weight gain
• Alopecia
• Pancreatitis
• Behaviour disturbance
• Fulminant hepatitis (rare)

MUST NOT BE USED IN PREGNANCY!!

Question 26

Idiosyncratic SE’s of clonazepam

Answer 26

• Behaviour disturbance
• Increased bronchial and salivary secretions

Question 27

What are idiosyncratic SEs of topiramate?

Answer 27

• Kidney stones
• Weight loss
• Speech disturbance
• Oligohydrosis/hyperthermia

Question 28

What are idiosyncratic SEs of levetiracetam?

Answer 28

• Behaviour disturbance

Question 29

What are idiosyncratic SEs of oxcarbazepine?

Answer 29

• Rash
• Hyponatremia

Question 30

What are idiosyncratic SEs of vigabatrin?

Answer 30

• Peripheral vision impairment
• Behaviour disturbance
• Weight gain

Question 31

What are idiosyncratic SEs of phenobarbital?

Answer 31

• Rash
• Behaviour disturbance

Question 32

Describe the clinical picture of post infectious cerebelitis.

Answer 32

• Acute cerebellar ataxia occurs primarily in children 1-3 years of age, and is a diagnosis of exclusion.
• It often follows a viral illness such as varicella, coxsackievirus, or echovirus by 2-3 weeks, and is thought to be due to an autoimmune response to the viral agent affecting the cerebellum.
• Post-infectious cerebellitis is sudden, and the truncal ataxia can be so severe that the child can’t stand or sit.
• Vomiting may occur initially, horizontal nystagmus is present in ~50% of cases, and dysarthria can be present. Resolution is usually complete by a few weeks to 2 months.

Question 33

What are the most common presenting signs of MS?

Answer 33

unilateral weakness with upper motor neuron signs, sensory abnormalities, visual complaints (with sudden loss of vision secondary to optic neuritis) or ataxia.

The diagnosis may be suspected after the first episode, but may not be confirmed until a second clinical episode occurs after a month or a new white lesion appears on MRI after 3 months.
•The pathophysiology involves demyelination and plaque formation.
•Short of biopsy or autopsy findings, the diagnosis can be confirmed with MRI showing the presence of small plaques in the brain stem and spinal cord. The CSF often also contains oligoclonal bands.
•Treatment with high dose methylprednisolone can quicken recovery, but does not appear to alter the long-term course of the disease.
•Optic neuritis may be the first presentation of MS and aggressive treatment of optic neuritis with prednisone does appear to decrease the long-term risk of MS.
•Interferon therapies can have a disease modifying effect.
•The prognosis of childhood MS is similar to that of adult disease. The recovery is often complete with slow progression of disease and long periods of remission in most cases.

Question 34

This child is hypotonic.

What is the diagnosis?

Answer 34

Pompe Disease

Question 35

Which AED should not be used in absence seizures or myoclonus?

Answer 35

Carbamazepine, it increases frequency of both.

Question 36

What is this lesion?

Answer 36

Brain abscess

Question 37

What is this lesion?

Answer 37

Cerebellitis

Question 38

What is this lesion?

Answer 38

Craniopharyngeoma

Question 39

What is this lesion?

Answer 39

Disseminated encephalomyelitis

Question 40

What is this lesion?

Answer 40

Pontine Glioma

Question 41

Describe Lennox-Gastaut Syndrome?

Answer 41

Triad of:

1. Developmental delay
2. Multiple seizure types that include atypical absences, and myoclonic, astatic, and tonic seizures.
3. EEG findings: 1-2 Hz spike–and-slow waves, polyspike bursts in sleep, and a slow background in wakefulness.

• Typically starts between the age of 2 and 10 yr
• The tonic seizures occur either in wakefulness (causing falls and injuries) or also, typically, in sleep.
• Most pts are left with long-term mental retardation and intractable seizures despite multiple therapies.

Myoclonic astatic epilepsy is a syndrome similar to but milder than Lennox-Gastaut syndrome that usually does not have tonic seizures or polyspike bursts in sleep. The prognosis is more favorable than that for Lennox Gastaut syndrome.

Question 42

What are the features and treatment of West Syndrome?

Answer 42

Epileptic encephalopathy which is most common epileptic syndrome in infancy. Requires urgent diagnosis, investigation and treatment.

1. Epileptic spasms
2. Hypsarrhythmia
3. Developmental delay

Epileptic spasms

• Brief tonic seizures that typically occur in a series over a minute or more, usually many times a day.
• Onset usually 3-8 months of age.
• Males > females
• Salaam (flexor) spasms most common - drawing up of legs, hunching forward of neck and shoulders and flinging out of arms.
• Opisthotonic or extensor spasms less common.

Hypsarrhythmia

• EEG shows diffusely disorganised pattern with high-voltage, multifocal epileptic activity (see image).

Developmental Delay

• May be delayed prior to onset of seizures
• May be loss of visual attention and arrest or regression of development at seizure onset.

Treatment

Corticosteroids (PO prednisolone or IM ACTH) best for rapid cessation of spasms. Also better neurological outcome in patients with no identified predisposing condition.

Vigabatrin second line (first line in tuberous sclerosis).

Question 43

Describe the clinical features, EEG pattern and treatment of absence epilepsy.

Answer 43

Usually present after age 4 years.

Two main syndromes:

1. Chilhood absence epilepsy - begins before age 10 yrs, tonic-clonic rare, good prognosis for seizure remission.
2. Juvenile absence epilepsy - later onset, sometimes teen years. Sometimes associated tonic-clonic seizure and prognosis poorer for seizure remission.

Seizures

• Sudden cessation of activity with staring, usually lasting only 5-15 seconds.
• Blinking, upward deviation of eyes, slight mouthing and fidgeting hand movements (automatisms) may occur.
• Unresponsive, does not fall, rarely incontinent, return promptly to normal activity at offset of absence with no memory of seizure.

EEG

• Childhood absence - Runs of generalised 3-Hz spike-wave activity
• Juvenile absence - faster and more irregular spike-wave activity.

Treatment

• Sodium valproate (epilim), ethosuximide (zarontin) and lamotrigine (lamictal) most commonly used Rx.
• Treatment for 2 years in CAE with expectation of seizure remission.
• Treatment through puberty into teen years in JAE.
• Rare refractory cases may respond to ketogenic diet.

Question 44

Descripe clinical features, EEG pattern and treatment of benign rolandic epilepsy (benign childhood epilepsy with centrotemporal spikes BCECTS)

Answer 44

Common epileptic syndrome in children. Occurs in otherwise normal primary school-aged children. Manifest with infrequent sleep-related focal seizures. Seizure and EEG focus in low in the central sulcus.

Cause is unknown with no underlying structural brain lesions and no evidence indicating genetic association.

Seizures

• Onset between 5-10 years
• Male predominance
• Focal seizures feature tingling or twitching of the mouth, preserved consciousness.
• Often associated with drooling, choking noises and inability to speak.
• May progress to jerking of one side of body, with our without impaired consciousness.
• Typically occur from sleep.

EEG

• Frequent focal epileptiform activity over the centrotemporal regions on one or both sides.

Treatment

• Treatment with antiepileptic medication is not always necessary as seizures are infrequent and many children only have one or two in total, and occurance is usually nocturnal.
• Treatment with sodium valproate (epilim) or carbamazepine (tegretol) for 1-2 years.

Excellent prognosis, without cognitive and behavioural problems and remission of seizures by teenage years.

Question 45

Describe the clinical features, EEG pattern and treatment of Benign Occipital Epilepsy.

Answer 45

Common epileptic sydrome in children occuring mostly in preschool age. Seizure and EEG focus in occipital region.

Clinical Features

• Presentation usually before 6 years
• Female predominance
• Focal seizure characteristically from sleep, beginning with staring, vomiting, head rotation, eye deviation and may lead to hemiclonic or bilateral jerking.
• Daytime attacks may occur with episodic visual distortions or hallucinations and migraine-like headaches.

EEG

• Focal epileptiform activity over the occipital regions

Treatment

• Treatment with antiepileptic medication is not always necessary as seizures are infrequent and many children only have one or two in total, and occurance is usually nocturnal.
• Treatment with sodium valproate (epilim) or carbamazepine (tegretol) for 1-2 years.

Excellent prognosis, without cognitive and behavioural problems and remission of seizures by teenage years.

Question 46

Describe the clinical features and treatment in Temporal Lobe Epilepsy.

Answer 46

Seizures

• Motionless staring, fearful or bewildered facial expression, unresponsiveness, hand and mouth movements that resemble voluntary actions (automatisms) and postictal amnesia and confusion.
• In some patients, may be head turning or stiffening or jerking of the limbs on one side during the seizure.
• Autonomic disturbances - facial flushing or pallor, salivation and vomiting - may occur.
• Apnoea may be predominant manifestation in infancy.
• Aura often present. Young or developmentally delayed children may describe as fear, unusual smells or tastes, abdominal discomfort and dizzy or dreamy states.
• Seizures last 30-60 seconds (longer than absence seizures) and are followed by postictal confusion and sleepiness.
• Occur in clusters over several days, alternating with seizure free periods.

Treatment

• Carbamazepine (tegretol) first drug of choice for epilepsies with focal seizures.

Question 47

Describe the clinical features of breath holding attacks.

Answer 47

• Usually start in 1st or 2nd year of life
• Up to 4% of children
• Attacks are precipitated by physical or emotional trauma
• Usually commence with crying, but may be brief or absent
• Apnoea and bradycardia occur, suddenly or gradually, with cyanosis or pallor following.
• Attack may terminate without LOC
• Attack may progress with LOC, limp and sometimes brief stiffening and jerking in response to cerebral ischaemia.
• Attacks usually cease by 3rd year of life.
• Iron-deficiency anaemia is an exacerbating factor in some children.

Question 48

Describe Landau-Kleffner syndrome

Answer 48

1. Sudden or gradual development of aphasia
2. Seizures in 70%
3. Sleep EEG shows epileptiform activity +++ (ESES - electrographic status epilepticus of sleep)

Age of onset usually 3-7 years

Question 49

Describe juvenile myoclonic epilepsy

Answer 49

Benign epilepsy usually presenting in teenage years.

Begins with myoclonic jerks, worse in the morning or shortly before falling asleep. Arms moreso than legs.

Clusters of myoclonus can lead to absence seizures, and clusters of absence seizures can lead to GTC.

Question 50

How can you distinguish benign neonatal sleep myoclonus from a seizure?

Answer 50

The clonus will continues if held or position change, but will cease when woken.

Question 51

Describe parasomnia

Answer 51

Parasomnia
 Parasomnias are defined as episodic nocturnal behaviors that often involve cognitive disorientation and autonomic and skeletal muscle disturbance. Parasomnias may be further characterized as occurring primarily during NREM sleep (partial arousal parasomnias) or in association with REM sleep, including nightmares, hypnogogic hallucinations, and sleep paralysis; other common parasomnias include sleep-talking. Partial arousal parasomnias, which include sleepwalking, sleep terrors, and confusional arousals are more common in preschool and school-aged children because of the relatively higher percentage of SWS in younger children. Any factor that is associated with an increase in the relative percentage of SWS (certain medications, previous sleep deprivation) may increase the frequency of events in a predisposed child. There appears to be a genetic predisposition for both sleepwalking and night terrors. In contrast, nightmares, which are much more common than the partial arousal parasomnias but are often confused with them, are concentrated in the last third of the night, when REM sleep is most prominent. Partial arousal parasomnias may also be difficult to distinguish from nocturnal seizures.
 Many children (15-40%) sleepwalk on at least one occasion; the prevalence of children who regularly sleepwalk is approximately 17%, and 3-4% have frequent episodes. Sleepwalking may persist into adulthood, with the prevalence in adults of about 4%. The prevalence is approximately 10 times greater in children with a family history of sleepwalking. Approximately 1-6% of children experience sleep terrors, primarily during the preschool and elementary school years, and the age of onset is usually between 4 and 12 yr. Because of the common genetic predisposition, the prevalence of sleep terrors in children who sleepwalk is about 10%. Although sleep terrors can occur at any age from infancy through adulthood, most individuals outgrow sleep terrors by adolescence. Confusional arousals commonly co-occur with sleepwalking and sleep terrors; prevalence rates have been estimated to be upwards of 15% in children ages 3-13 yr.
 The partial arousal parasomnias have several features in common. Because they typically occur at the transition out of “deep” or SWS, partial arousal parasomnias have clinical features of both the awake (ambulation, vocalizations) and the sleeping (high arousal threshold, unresponsiveness to the environment) states; there is usually amnesia for the events. The typical timing of partial arousal parasomnias during the first few hours of sleep is related to the predominance of SWS in the first third of the night; the duration is typically a few minutes (sleep terrors) to an hour (confusional arousals). Sleep terrors are sudden in onset and characteristically involve a high degree of autonomic arousal (i.e., tachycardia, dilated pupils), while confusional arousals typically arise more gradually from sleep, may involve thrashing around but usually not displacement from bed, and are often accompanied by slow mentation on arousal from sleep (“sleep inertia”). Sleepwalking may be associated with safety concerns (e.g., falling out of windows, wandering outside). Avoidance of, or increased agitation with, comforting by parents or attempts at awakening are also common features of all partial arousal parasomnias.