Neurology Flashcards
What is cerebral palsy?
A static encephalopathy
How often is intrapartum hypoxia the cause of CP?
10% of cases
What are the types of CP in order of commonness?
Spastic (90%)
Dyskinetic (6%)
Ataxic (4%)
How common is cerebral palsy?
2 in 1000
What kind of lesion causes spastic CP?
UMN - usually periventricular leukomalacia
What are the clinical features of spastic CP?
Velocity dependent spasticity
Brisk deep tendon reflexes
Extensor plantar responses
What are the three subtypes of spastic CP?
Hemiplegia
Quadriplegia
Diplegia
What are the clinical features of dyskinetic CP?
Involuntary movements
Chorea
Athetosis
Dystonia
What is athetosis?
Slow, writing movements
What kind of lesion causes dyskinetic CP?
Mostly HIE
What lesions can cause ataxic CP?
Mostly genetic
If brain injury, signs are on the same side as the lesion
What are the clinical features in ataxic CP?
Early trunk and limb hypotonia
Poor balance
Later incoordinate movements, intention tremor and ataxic gait
How is cerebral palsy diagnosed?
Clinical
MRI
EEG if seizures
Which conditions are associated with CP?
Intellectual impairment (50%) Epilepsy (45%) Speech and language disorders Ophthalmological defects Hearing impairment
How is CP managed?
Gabapentin
Botox for hypertonicity
Intrathecal baclofen
Selective dorsal rhizotomy
What is baclofen?
GABA analogue
What features do frontal seizures have?
Clonic movements
Asymmetrical tonic seizures
Atonic
What features can temporal lobe seizures have?
Strange warning feelings or aura Lip smacking Plucking at a clothing Walking in a non-purposeful manner Deja vu and jamais vu
What features might an occipital lobe seizure have?
Distortion of vision
What features can a parietal lobe seizure have?
Contralateral dysaesthesias
Distorted body image
When does West syndrome usually present?
4-6 months
What do the seizures in West syndrome look like?
Infantile spasms - violent flexing of the head, trunk and limbs followed by extension of the arms
Which skills will be affected in West syndrome?
Often social first, but most will lose other skills too
How many children with West syndrome have an underlying neurological cause?
2/3
What does the EEG show in West syndrome?
Hypsarrhythmia - high voltage slow waves and multifocal sharp wave discharges
How is West syndrome treated?
Steroids, vigabatrin, sometimes ACTH
How many respond to treatment in West syndrome?
30-40%
What is the prognosis for West syndrome?
Most will develop a learning disability or epilepsy
When does Lennox-Gastaut syndrome usually present?
1-3 years
What kind of seizures are seen in Lennox-Gastaut syndrome?
Drop attacks
Tonic seizures
Atypical absences
How is development affected in Lennox-Gastaut syndrome?
Neurodevelopmental arrest or regression
Behavioural disorder
What is the prognosis like in Lennox-Gastaut syndrome?
Poor - many relate to a pre existing or other complex neurological disorder
When does childhood absence epilepsy usually present?
4-12 years
How is development affected in childhood absence epilepsy?
Usually not affected, but can interfere with schooling
Does childhood absence epilepsy affect more girls or boys?
2/3 are female
How can seizures be induced in childhood absence epilepsy?
Hyperventilation
What does the EEG show in childhood absence epilepsy?
Generalised 3Hz spike and wave discharge, bilaterally synchronous during and sometimes between episdoes
What’s the prognosis for childhood absence epilepsy?
Good
What drugs can be used in childhood absence epilepsy?
Sodium valproate
Ethosuximide
Lamotrigine
What does BECTS stand for?
Benign epilepsy with centrotemporal spikes
When does BECTS usually present?
4-10 years
What kind of seizures are seen in BECTS?
Tonic clonic seizures in sleep
Simple focal seizures with awareness of abnormal feelings in the tongue and distortion of the face
May involve the vocal tract with guttural sounds, hemifacial sensorimotor symptoms, hypersalivation and speech arrest
What does the EEG show in BECTS?
Focal sharp waves from the Rolandic or centrotemporal area
What is the management for BECTS?
Might not even need treatment - almost all remit in adolescence
What is early onset benign childhood occipital epilepsy also known as?
Panayiotopoulous syndrome
When does Panayiotopoulous syndrome present?
1-14 years
How does Panayiotopoulous syndrome present in younger children?
Periods of unresponsiveness, eye deviation, vomiting and autonomic features
How does Panayiotopoulous syndrome present in older children?
Headache and visual disturbance, distortion of images, hallucinations; can have syncope-like unresponsiveness and behaviour change
What might the seizures in Panayiotopoulous syndrome lead to?
Autonomic status
Hemiconvulsions or generalised convulsions
What does the EEG show in Panayiotopoulous syndrome?
Interictal EEG shows multifocal, high amplitude, sharp and slow-wave complexes
What is the prognosis in Panayiotopoulous syndrome?
Remits in childhood with AEDs rarely needed
When does juvenile myoclonic epilepsy present?
Adolescence-adulthood
What kind of seizures are seen in juvenile myoclonic epilepsy
Myoclonic
But GTCs and absences can occur, mostly shortly after waking
What does the EEG show in juvenile myoclonic epilepsy?
3-6Hz generalised polyspike and wave discharge
What’s the prognosis in juvenile myoclonic epilepsy?
Remission unlikely, but tends to respond to treatment
What drugs can be used in juvenile myoclonic epilepsy?
Sodium valproate
Benzodiazepines
Lamotrigine
Which drug can worsen seizures in juvenile myoclonic epilepsy?
Carbamazepine
What are 2 common mutations causing neonatal seizures?
ERBBB4, SCN1A
When do genetically caused neonatal seizures tend to present?
Before day 10
What is the clinical triad for genetic neonatal seizures?
Myoclonius
Then focal fits
Then tonic infantile spasms
What’s the prognosis for neonatal genetic seizures?
Very poor - devastating psychomotor and developmental regression, bilateral pyramidal signs
Wat is Ohtahara syndrome?
A syndrome causing seizures in the neonatal period with many causes; age-dependent reaction to an insult that can progress to West syndrome or Lennox-Gastaut
Which cerebral malformations can cause Ohtahara syndrome?
Aicardi Linear sebaceous naevus syndrome Porencephaly Hemimegaloencephaly Focal cortical dysplasia Cerebral dysgenesis
What are the two main genetic causes of Ohtahara syndrome?
GLUT1 deficiency syndrome
MECP2 mutation
What are the clinical features of Ohtahara syndrome?
Tonic spasms lasting 1-10 seconds, often in clusters up to 100 times per day
What does the EEG show in Ohtahara syndrome?
Burst suppression
What ist he prognosis for Ohtahara syndrome?
50% mortality in weeks or months; survivors have severe cognitive/neurological deficits
How can Ohtahara syndrome be treated?
No AED consistently effective - can also try vitamins or surgery
How are benign familial seizures inherited?
Autosomal recessive
When is the onset of benign familial seizures?
Day 4-7
What are the clinical features of benign familial seizures?
Brief seizures
Can involve apnoea, deviation of head/eyes, tonic-clonic, autonomic changes
What is the prognosis for benign familial seizures?
Tend to remit in days-months, normal intelligence long-term
How can benign familial seizures be treated?
Acute: phenobarbitone, benzodiazepines, phenytoin
Preventative: keppra, valproate, carbamazepine
What are the commonest causes of early myoclonic encephalopathy?
Inborn errors of metabolism Non-ketotic hyperglycinaemia Menkes disease Zellweger syndrome Methylmalonic acidaemia
Which is an important treatable cause of early myoclonic encephalopathy?
Pyridoxine-dependent epilepsy, which will respond well to pyridoxine supplementation
When do malignant migrating partial seizures in infancy present?
3 months
What kind of seizures are seen in malignant migrating partial seizures in infancy?
Mutlifocal - tonic and/or clonic, can have autonomic features
Frequent, almost continuous seizures
What other problems are malignant migrating partial seizures in infancy associated with?
Psychomotor regression
Quadriplegia
What is the prognosis in malignant migrating partial seizures in infancy?
Poor - most AEDs are ineffective and may die by 12 months
What is Fukuyama-Watanabe-Vigevano syndrome also called?
Benign familial infantile seizures and non-familial infantile seizures
What is the difference between the familial and non-familial form of Fukuyama-Watanabe-Vigevano syndrome?
Not much - other than that the non-familial forms’ gene abnormalities occur de novo and familial cases may have longer fits with altered consciousness, motor arrest, clonic seizures, automatisms
When does Fukuyama-Watanabe-Vigevano syndrome present?
5 months
What kind of seizures are seen in Fukuyama-Watanabe-Vigevano syndrome?
Focal, brief diurnal seizures that occur in clusters of -10 daily for 1-3 days, then recur in 1-3 months
When does myoclonic epilepsy of infancy usually present?
6 months-3 years
What kind of seizures are seen in myoclonic epilepsy of infancy?
Myoclonic jerks which are spontaneous or reflex, usually with head nodding and upper limbs flinging outward. Brief duration often with intact consciousness
What can myoclonic epilepsy of infancy be treated with?
Valproate
What is the defect behind benign familial neonatal-infantile seizures?
Sodium channelopathy
When do benign familial neonatal-infantile seizures usually present?
2 days to 7 months
What kind of seizures are seen in benign familial neonatal-infantile seizures?
Focal
What is the prognosis for benign familial neonatal-infantile seizures?
Can resolve by 12 months
Which AEDs are used for myoclonic epilepsy in non progressive disorders e.g. Prader-Willi
Valproate
Benzodiazepines
Ethosuximide
ACTH
What is Dravet syndrome also known as?
Severe myoclonic epilepsy of infancy
What mutation is Dravet commonly associated with?
SCN1A
When is the usual onset of Dravet syndrome?
6 months
What seizures are seen in Dravet syndrome?
Status Hemimotor status plus pallor, automatisms Clusters of absences Head turning and flexed upper limbs Myoclonic by 4 years Atonic seizures Non-convulsive status
What can be the precipitants for seizures in Dravet syndrome?
Visual induced
Hyperthermia
Water
Carbamazepine
How does Dravet affect development?
Normal development initially followed by developmenta/neurocognitive regression, with evolving ataxia and pyramidal signs
Which AEDs can be used in Dravet?
Valproate Topiramate Clobazam Keppra Stiripentol Cannabidiol
What is Doose syndrome also known as?
Epilepsy with myoclonic-atonic seizures
How commonly is there a family history of seizures in Dose syndrome?
Family history of febrile seizures in 50%, epilepsy in 1/3
When is the usual onset of Doose syndrome?
6 months to 6 years
Is Doose syndrome more common in girls or boys?
Boys
Which kinds of seizures are seen in Doose syndrome?
Febrile and afebrile GTCs
Months later, myoclonic-atonic seizures
Can have pure atonic or absence, and non-convulsive status
1/3 have status at some point
What is Gastaut type epilepsy also known as?
Late-onset childhood occipital epilepsy
What is Gastaut type epilepsy?
A self-limiting childhood seizure susceptibility syndrome
What kind of family history is there in Gastaut type epilepsy?
Epilepsy or migraine
When is the usual onset of Gastaut epilepsy?
15 months to 19 years
What kind of seizures are seen in Gastaut type epilepsy?
Pure occipital seizures with visual hallucinations (e.g. confetti or sequins), blindness or a combination
Short duration, frequent
Preserved consciousness
Can have other features e.g. head turning, blinking
What does the interictal EEG show in Gastaut type epilepsy?
Occipital paroxysms
What is the AED of choice in Gastaut type epilepsy?
Carbamazepine
What can develop if Gastaut type epilepsy isn’t treated?
GTCs
How common is a family history in epilepsy with myoclonic absences?
1/5
When is the usual onset of epilepsy with myoclonic absences?
1-12 years
Does epilepsy with myoclonic absences affect more boys or girls?
Boys
What are the clinical features of epilepsy with myoclonic absences?
Rhythmic Myoclonic jerks with tonic contraction, usually unilateral Impairment of consciousness Short Frequent >75% will have another seizure type
What does the EEG show in epilepsy with myoclonic absences?
Generalised or multifocal spike and slow wave
How many children with epilepsy with myoclonic absences will have a learning disability?
70%
What’s the prognosis like in epilepsy with myoclonic absences?
Often difficult to treat
What kind of seizures is carbamazepine useful for?
Partial seizures
GTCs
What are the side effects of carbamazepine?
Ataxia Sedation Leukopenia Thrombocytopenia Rash
Which seizures is sodium valproate useful for?
All
What are the side effects of sodium valproate?
Nausea and vomiting Abdo pain Tremor Hair loss Thrombocytopenia LFT abnormalities
Which seizures is lamotrigine useful for?
All
What are the side effects of lamotrigine?
Rash
What kinds of seizures is vigabatrin useful for?
Partial seizures
West syndrome
What are the side effects of vigabatrin?
Sedation
visual field constriction
What kind of seizures is ehtosuximide useful for?
Absences
What are the side effects of ethosuximide?
GI disturbance
Rash
Which kind of seizures is gabapentin useful?
Partial
What are the side effects of gabapentin?
Sedation
Which kind of seizures is oxcarbazpine useful for?
Partial/generalised
What are the side effects of oxcarbazepine?
Sedation
Rash
What kind of seizures is topiramate useful for?
All
What are the side effects of topiramate?
Sedation
Anorexia
Paraesthesiae
What kind of seizures are clobazam and clonazepam useful for?
All
What are the side effects of clobazam and clonazepam?
Sedation
What kind of seizures is phenytoin useful for?
All
What are the side effects of phenytoin?
Nausea and vomiting
Diarrhoea
Rash
Peripheral neuropathy
What kind of seizures is phenobarbital useful for?
All
What are the side effects of phenobarbital?
Sedation
What kind of seizures is keppra useful for?
Partial
What are the Side effects of keppra?
Sedation
What kind of seizures is tiagabine useful for?
Partial
What are the side effects of tiagabine?
Sedation
What is the management of status?
2x benzos
Rectal paraldehyde
Phenytoin
RSI
How many neural tube defects are preventable with maternal folate supplementation?
70%
What are some non-folate causes of neural tube defects?
High BMI Temperature elevation Diabetes Anti epileptics T13, 18 and 21 Waardenburg syndrome Joubert syndrome type 1
What is the risk of recurrence for a mother who has had a child with a neural tube defect?
1 in 100-200; triple the baseline risk
What are the different kinds of neural tube defects?
Spina bifida occulta Anencephaly Encephalocoele Meningocoele Myelomeningocoele
What is the defect in spina bifida occulta?
Failure of closure of the vertebral arch
What is the defect in anencephaly?
Failure of closure of the rostral aspect of the neural tube
What is the prognosis in anencephalic pregnancies?
75% will be stillborn
What is the defect in an encephalocoele?
Protrusion of cerebral tissue through midline cranial defect located in frontal or occipital regions
What is the defect in meningocele?
Cyst formed by herniation of meninges, usually over dorsum of spine
What are the possible sequelae of a meningocoele
Neurological disability is minimal, but risk of bacterial meningitis
What is the defect in a myelomeningocoele?
Herniation of meninges, nerve roots, and spinal cord through the dorsal vertebral defect
What are the possible sequelae of a myelomeningocoele?
Motor and sensory defects below the lesion, including sphincter disturbance
Hydrocephalus can occur
What particular malformation might be associated with a myelomeningocoele?
Arnold-Chiari
What are the options for bladder dysfunction from neural tube defects?
Anticholinergics
Alpha adrenergics
Intermittent catheterisation
Botox
What are the features of the Arnold-Chiari II malformation?
Downward displacement of the cerebellar tonsils and vermis through the foramen magnum
Elongation and kinking of the medulla
Caudal displacement of the cervical spinal cord and medulla
Obliteration of the cisterna magna
What are the possible consequences of an Arnold-Chiari II malformation?
Descent of hindbrain through foramen magnum - can cause compression of brainstem, cerebellar dysfunction, medullary respiratory centre dysfunction, malfunction of IX and X nerves, hydrocephalus
What are the clinical features of an Arnold-Chiari II malformation?
Swallowing problems GORD Dysarthria OSA Stridor Weakness or spasticity of upper limbs Clumsiness or poor coordination Many others!
How is the Arnold-Chiari II malformation managed?
Surgically:
Decompression of the medulla and upper cervical cord
Insertion of a dural patch to increase the size of the dural sac
Cervical laminectomy
What is a syringomyelia?
Cavity which communicates with the central canal of the spinal cord
With is hydromyelia?
Dilatation of the central canal of the spinal cord
What malformation is associated with Syringohydromyelia?
ArnoldChiari II
What clinical features are associated with Syringohydromyelia?
Scoliosis
Lower limb weakness and deformities
Upper limb weakness
Back pain
How can a syringohydromyelia be treated?
Shunt from syrinx to peritoneal cavity
What are the causes of scoliosis in myelomeningocele?
Congenital malformation Syringohydromyelia Tethered cord Shunt failure Spinal muscle weakness
How common is tethered cord in myelomeningocele?
Present in virtually all, but only causes problems requiring intervention in 1/3
What are the symptoms of tethered cord?
Often during growth spurts Gait changes (crouched) Back or lower limb pain Worsening of motor function Change in sensory level Change in bladder or bowel habit Progressive deformity of spine or lower limbs
How is spinal muscle atrophy inherited?
Autosomal recessive
What gene is responsible for spinal muscular atrophy?
5q11-13
What is the defect in spinal musuclar atrophy?
Degeneration of anterior horn cells due to mutation in the survival motor neurone gene
What is the general clinical picture in spinal muscular atrophy?
Progressive weakness and wasting of skeletal muscles
What is SMA Type 1 also known as?
Werdnig-Hoffman disease
When does SMA type 1 present?
Antenatally as diminished foetal movements, or in early infancy
What signs might be seen in spinal muscular atrophy?
Arthrogryposis Lack of antigravity power in hips Symmetrical weakness, proximally>distally, trunk and limbs Absent deep tendon reflexes Intercostal recession Fasciculation of the tongue Unable to sit or walk
What is the prognosis of SMA type I?
Bad - death is from respiratory failure at about 10 months
When is the usual onset of SMA type II?
After 3 months
What are the clinical features of SMA type II?
Can sit but not walk
Prone to early scoliosis
What is the prognosis of SMA type II?
Depends on degree of respiratory muscle involvement
What is SMA type III also known as?
Kugelberg-Welander disease
What are the features of SMA type III?
Can walk, but some proximal weakness
Tendon jerks may not be absent
What is Charcot-Marie-Tooth disease also known as?
Peroneal muscular atrophy
What are the clinical features of Charcot-Marie-Tooth?
Slowly progressive distal weakness with areflexia
Foot drop often the main early problem
In later stages (up to decades later): hand weakness, joint deformity, distal sensory loss
What are the differences between Freidreich’s ataxia and HMSNs?
Areflexia in HMSN
More clear ataxia in Freidreich’s
HMSN have abnormal motor conduction, whereas Freidreich’s have sensory neuropathy
What are the three most common types of Charcot-Marie-Tooth?
1: demyelinating
2: axonal
3: hypertrophic
And X-linked forms
What are the features of type 1 charcot-Marie-Tooth?
Low motor neurone conduction velocity
1st decade onset
What are the features of type 2 Charcot-Marie-Tooth disease?
Normal motor neuron conduction velocity
2nd to 3rd decades
What are the features of type 3 Charcot Marie Tooth?
Low motor neurone conduction velocity
1st year onset
What is the most common disease of the NMJ?
Myasthenia gravis
What is the defect in myasthenia gravis?
Antibodies against postsynaptic acetylcholine receptors
What are the clinical features of myasthenia gravis?
Affects extra ocular muscles first, then proximal limbs and bulbar muscles
Weakness which gets worse over the course of the day
How is Myasthenia Gravis diagnosed?
Edrophonium test
EMG (confirms neuromuscular block)
Anti-ACh receptor antibodies
How is Myasthenia Gravis treated?
Anticholinesterases
Immunosuppressants
Thymectomy
Plasma exchange or IVIG
What is the cause of Sydenham chorea?
Immune reaction triggered by group A strep infection
What is the prognosis for Sydenham chorea?
75% have resolution of chorea within 6 months
What is the defect in anti-NMDA receptor encephalitis?
Antibodies to the NMDA receptor - usually after an intercurrent illness or mycoplasma infection
What are the clinical features of anti NMDA receptor encephalitis?
Movement disorder e.g. chorea, dystonia
Autonomic instability
Neuropsychiatric symptoms
Seizures
How do you treat anti-NMDA receptor encephalitis?
Steroids Immunoglobulin Plasma exchange Cyclophosphamide Rituximab
What is subacute sclerosis panencephalitis?
Slow viral infection caused by atypical response to measles infection
What are the risk factors for subacute sclerosis pan encephalitis?
Exposure to measles in first 2 years
Natural measles infection vs immunisation
What are the clinical features of subacute sclerosing panencephalitis?
Subtle deficits first
Increasing memory difficulties
Worsening disabilities: seizures, motor difficulties, learning disability
What is the median interval between measles and subacute sclerosis panencephalitis?
8 years
What is the gene for neurofibromatosis type 1?
NF1 gene on 17q11.2
What does the NF1 gene code for?
Neurofibromin 1, a cytoplasmic protein found throughout the nervous system
What are the diagnostic criteria for NF1?
Need 2 or more:
≥6 cafe au last spots, >5mm in prepubertal patients or >15mm in post pubertal patients
≥2 neurofibromas or one plexiform neurofibroma
Axillary or inguinal freckling
Optic glioma
≥2 iris hamartomas (Lisch nodules)
Typical osseous lesions e.g. sphenoid dysplasia
1st degree relative affected
What are the neurological manifestations of NF1?
Macrocephaly
Learning disability
Epilepsy
Optic gliomas
What are the non-diagnostic features of NF1?
Scoliosis
Hypertension
Pulmonary stenosis
Tumours: brainstem and cerebellar gliomas
Which gene codes for neurofibromatosis type 2?
NF2 gene on 22q11.2
What are the diagnostic criteria for neurofibromatosis type 2?
Bilateral 8th nerve neurofibromas
Unilateral 8th nerve mass in association with any 2 of : meningioma, neurofibroma, schwannoma, juvenile posterior capsular cataracts
Unilateral 8th nerve tumour or other spinal or brain tumour in 1st degree relative
How is tuberous sclerosis inherited?
Dominantly, with variable expression
Which mutations are responsible for tuberous sclerosis?
TSC1 (9p34) and TSC2 (16p), both of which are tumour suppressor genes
What are the clinical features of tuberous sclerosis?
Seizures Neurodevelopmental impairment Cutaneous manifestations Retinal hamartomas Renal angiolipomas Cardiac rhabdomyomas Brain: cortical tubers and subependymal nodules with calcifications
What are the cutaneous manifestations of tuberous sclerosis?
Adenoma sebaceum
Periungual fibromas
Hypopigmented patches
Shagreen patch
What are the characteristic features of ataxia telangiectasia?
Conjunctival telangiectasia
Progressive cerebellar degeneration
Immunological impairment
Where is the gene for ataxia telangiectasia?
11q22-23
What are the clinical features of ataxia telangiectasia?
Progressive ataxia
Scleral telangiectasia
Abnormality of cell mediated and humeral immunity, causing sinopulmonary infections, high incidence of reticuloendothelial malignancy
How is ataxia telangiectasia diagnosed?
Elevated alpha fetoprotein
Low IgA and IgD
Inversions and translocations on chromosomes 7 and 14
Gene mutation analysis
What are the features of Sturge Weber syndrome?
Port wine stain in the distribution of the trigeminal nerve
Facial naevus
Ipsilateral leptomeningeal angioma, causing ischaemic injury to underlying cerebral cortex
What are the consequences of Sturge Weber syndrome?
Focal seizures
Hemiparesis
Variable degree of intellectual deficit
Glaucoma (usually ipsilateral to the port wine stain)
How is incontinentia pigmenti inherited?
Probably X linked dominant; NEMO gene
What are the skin features of incontinentia pigmenti?
Erythematous papular, vesicular or bullous lesions on trunk and limbs
Then pustular lesions
Then pigmented
What are the non-skin features of incontinentia pigmenti?
30-50% have neurological features e.g. seizures, encephalopathy
30% have eye lesions
How is hypomelanosis of Ito inherited?
Sporadically
What are the features of hypomelanosis of Ito?
Hypopigmented areas that are streaky, patchy, or whorls
Seizurs
Hemimegalencephaly (one half of cerebral cortex larger than the other)
What is the defect in lishencephaly?
Brain has very few or no gyro, so the surface of the brain is smooth
What are the clinical features of lishencephaly?
Severe motor and learning disability
What are the associated mutations in lishencephaly?
65% associated with mutations in LIS1 gene
17p13.3 deletion - Miller-Dieker syndrome (facial abnormalities)
What is the defect in polymicrogyria?
Increased numbers of small gyro, especially in the temporoparietal regions. Can be focal or generalised
What is the defect in periventricular heterotopia?
Aggregation of neurone arrested in their primitive positions
What is pachygyria and what are the consequences?
Thickened, abnormal cortex - depending on extent can cause cerebral-palsy like picture or epilepsy
Which brain malformation is associated with Aicardi syndrome?
Agenesis of corpus callosum
What are the features of Moebius syndrome?
Bilateral facial paralysis with bilateral abducens paralysis
Other lower CNs can be affected
1/4 have learning disability
What are the features of Bell’s palsy?
Unilateral facial paralysis
What’s the cause of Bell’s palsy?
Usually idiopathic
What is the management of Bell’s palsy?
Usually recovers completely in 2-4 weeks, but steroids can be given
What are the clinical features of a 3rd nerve palsy?
Down and out position of the eye; can involve pupillary reaction if parasympathetic fibres are involved
What are the causes of a 3rd nerve palsy?
Closed head trauma, infection, tumour
What are the features of a 4th nerve palsy?
Superior oblique palsy, which pulls the eye downwards; vertical diplopia when looking obliquely, often head tilting, and torsional diplopia
What is the most common cause of a 4th nerve palsy?
Trauma
What is the most common cause of a 6th nerve palsy?
Raised ICP - tumours, benign intracranial hypertension
What are the features of a 6th nerve palsy?
Convergent squint and horizontal diplopia
What are the features of the classic Dandy-Walker malformation?
Complete or partial Genesis of cerebellar vermis
Large cystic formation in posterior fossa due to dilatation of fourth ventricle
Hydrocephalus (may not develop until adulthood)
What is a Dandy-Walker variant?
Part of vermis present, posterior fossa not enlarged
What is megacisterna magna?
Complete vermis, large retrocerebellar cyst
What is Joubert syndrome?
Familial agenesis of the cerebellar vermis
What are the features of Joubert syndrome?
Episodic hyperpnoea
Ataxia
Cognitive impairment
What is periventricular leukomalacia?
Bilateral necrosis of periventricular white matter with ensuing gliosis
What are the consequences of periventricular leukomalacia?
Interruption of the fibres responsible for lower limb and optic function –> spastic diplegia and visual impairment
Which nerves are affected in Erb’s palsy?
C5-6
Which muscles are affected in Erb’s palsy?
Deltoid Serratus anterior Supraspinatus Infraspinatus Biceps Brachioradialis
What are the clinical features of Erb’s palsy?
Arm is flaccid, adducted, and internally rotated
Elbow is extended, wrist flexed
Which nerves are affected in a Klumpke paralysis?
C8-T1
What are the features of a Klumpke paralysis?
Intrinsic hand muscles are affected leading to flexion of wrist and fingers
Cervical sympathetic involvement can lead to ipsilateral Horner syndrome
What is the defect in Friedreich’s ataxia?
Spinocerebellar degeneration - abnormality of a gene for frataxin, which is involved in modulation of mitochondrial function
How is Friedreich’s ataxia inherited?
Autosomal recessive
Where is the gene for Friedreich’s ataxia?
9cen-q21
What are the clinical features of Friedreich’s ataxia?
Onset 1st or 2nd decade Loss of proprioception Increasing impairment of cerebellar function Development of pis caves, nystagmus Cardiomyopathy Usually not ambulant by 20s or 30s
How is Friedreich’s ataxia treated?
Symptomatic
Physiotherapy
Antioxidant treatment e.g. idebenone may be of benefit in delaying cardiac deterioration
What is dystonia?
Abnormal muscle tone without pyramidal involvement
What is dystonia musculorum deforming also known as?
Torsion dystonia
How is torsion dystonia inherited?
Autosomal dominant with incomplete penetrance
What is the gene for torsion dystonia?
9q34 in Jewish families; another unidentified gene in others
When is the usual onset of torsion dystonia?
After 5 years
What are the clinical features of torsion dystonia?
Can be focal or generalised
Can be task specific e.g. when walking forwards but not backwards
Often gradually spreads to other parts of the body
How is torsion dystonia treated?
High dose anticholinergics
Sometimes L-dopa
What is the cause of dopa-responsive dystonia?
Idiopathic
What are the clinical features of dopa-repsonsive dystonia
Can start in first 5 years
Symptoms vary throughout the day
Where is the gene for dopa-responsive dystonia?
14q22.1-q22.2
How is dopa responsive dystonia treated?
Lifelong L-dopa
What is the most common cause of childhood muscular dystrophy?
Duchenne
What is the defect in Duchenne muscular dystrophy?
Mutation in the dystrophin gene on the X chromosome
What is the natural history of Duchenne?
Diagnosis around 5 years Delayed motor milestones Proximal skeletal muscle weakness Waddling gait Difficulty climbing stairs Motor regression Wheelchair bound by 12 Decline in respiratory function and cardiomyopathy
What is the life expectancy in Becker muscular dystrophy?
67
When does wheelchair dependency happen in Becker?
between 3rd and 7th decade
How is Duchenne inherited?
X-linked recessive, but 1/3 are de novo mutations
How common is Duchenne?
1 in 3600-6000 male births
What is the defect in Duchenne?
Absence of dystrophin makes the muscle membrane vulnerable from shearing stresses, leading to degeneration of muscle fibres
How is Duchenne diagnosed?
Array CGH
Next generation sequencing
Muscle biopsy
Prenatal diagnosis with CVS or amnio also possible
What are the examination findings in Duchenne
Small muscle bulk Pseudohypertrophy of calves Equinus deformity of feet Gait abnormalities Gower's manoeuvre Proximal weakness
Which gait abnormalities might be seen in Duchenne?
Knee-locking gait
Trendelenburg gait
Lordosis
Easier to walk on toes than heels
What is a Trendelenburg gait?
Weak hip flexors mean the leg is swung forward, and the pelvis tilts down on the unsupported side
What is the instruction for Gower’s manoeuvre?
Ask to lie supine then get up
How is Duchenne managed?
Steroids Physio OT Surgery as needed for fractures, tonotomies, scoliosis NIV ACE inhibitors or beta blockers
How is Emergy-Dreifuss muscular dystrophy inherited?
X-linked; Xq28
What are the features of Emery-Dreifuss muscular dystrophy?
Mild proximal muscular weakness
Joint contractures
Cardiac involvement and sudden cardiac death
How is facioscapulohumeral muscular dystrophy inherited?
AD - 4q35
What are the features of facioscapulohumeral muscular dystrophy?
Facial, scapular, humeral wasting and weakness
Slowly progressive
Other muscles can be involved
Variable expression within families
What are the features of merosin-negative congenital muscular dystrophy?
Hypotonia Weakness Contractures Learning disability Don't achieve independent walking Absence of Mersin on muscle biopsy
What is the difference between merosin-positive muscular dystrophy and merosin-negative?
Similar but merosin-positive is less severe
What are the clinical features of congenital muscular dystrophies associated with abnormal glycosylation of alpha-dystroglycan?
Severe weakness
Brain malformations
What are some examples of congenital muscular dystrophies associated with abnormal glycosylation of alpha-dystroglycan?
Fukuyama congenital muscular dystrophy
Muscle-eye-brain disease
Walker-Warburg syndrome
How is myotonic dystrophy inherited?
AD
What are the features of congenital myotonic dystrophy?
Often unrecognised in mothers May have preceding polyhydramnios Facial weakness, hypotonia Often needing respiratory support Joint contractures, especially talipes
What are the features of myotonic dystrophy in older children?
Initially facial weakness
Then weakness affecting temporals, sternomastoid, distal leg muscles
Progressive weakness
Difficulty in relaxing muscular contraction
Cardiac involvement
How is myotonic dystrophy diagnosed?
Gene mutation analysis
Electromyogram (‘dive bomber’ discharges)
What is Thomsen disease also known as?
Myotonia congenita
What are the features of myotonia congenita?
Myotonia
Cramps
Muscular hypertrophy
What does biopsy show in Charcot Marie Tooth?
Onion bulb - due to demyelination followed by attempts at remyelination
What does the CSF show in Guillain Barre
Raised protein, normal white cell count
What is cranial nerve 1?
Olfactory
Is the olfactory nerve sensory or motor?
Sensory only
How do you test the olfactory nerve?
Ask about sense of smell, smell a mint
What is cranial nerve 2?
Optic
Is the optic nerve motor or sensory?
Sensory only
How do you examine the optic nerve
Pupil size, shape, symmetry Visual acuity Direct and consensual pupillary response Swinging torch Accommodation reflex Colour vision Visual inattention Blind spot Visual fields
What is cranial nerve 3?
Oculomotor
What is cranial nerve 4?
Trochlear
What is cranial nerve 6?
Abducens
What does oculomotor supply?
All extra ocular muscles except superior oblique and lateral rectus
Parasympathetic fibres for pupillary constriction
What does the trochlear nerve supply?
Superior oblique
What does abducens supply?
Lateral rectus
How do you examine oculomotor, trochlear, and abducens nerves?
Ptosis
Squint/nystagmus
Eye movement through horizontal and vertical planes
What is cranial nerve 5?
Trigeminal
What are the branches of the trigeminal and are they sensory or motor?
Ophthalmic - sensory
Maxillary - sensory
Mandibular - sensory and motor
How do you test the trigeminal nerve?
Sensation over forehead, cheek and jaw
Clench teeth and waggle jaw against resistance
Jaw jerk and corneal reflexes
What is cranial nerve 7?
Facial
Is the facial nerve motor or sensory?
Motor to facial expression and stapedius
Sensory to anterior 2/3 of the tongue
How do you test the facial nerve?
Ask about change in taste or hearing Facial asymmetry Raise eyebrows Close eyes tight Blow out cheeks Smile Pursed lips
What is cranial nerve 8?
Vestibulocochlear
Is the vestibulocochlear nerve sensory or motor?
Sensory only
How do you test the vestibulocochlear nerve?
Ask about hearing
Weber and Rinne
What is the 9th cranial nerve?
Glossopharyngeal
What is the 10th cranial nerve?
Vagus
What does the glossopharyngeal nerve supply?
Motor for swallowing and speech
Sensory for posterior 1/3 of tongue
What does the vagus nerve supply?
Motor to muscles involved in speech and gag reflex
How do you test the glossopharyngeal and vagus nerves?
Ask about swallowing, drooling, speech and cough
Say ‘aah’ look at uvula for deviation
Gag reflex
What is the 11th cranial nerve?
Accessory
Is the accessory nerve sensory or motor?
Motor
How do you test the accessory nerve?
Trapezius and sternomastoid - shrug shoulders and turn head against resistance
What is the 12th cranial nerve?
Hypoglossal
Is the hypoglossal nerve motor or sensory?
Motor
How do you test the hypoglossal nerve?
Stick tongue out, look for atrophy or deviation
Push tongue into each cheek
