Neurology 2 Flashcards
Overview/presentation of acute cerebellar ataxia
Most common cause of ataxia, usually post infection
Ataxia develops over hours to days after illness
- nystagmus, slurred speech, difficulty with fine motor movements, truncal titration, gait instability
Should NOT have altered mental status, seizures or meningismus
Investigation/management of acute cerebellar ataxia
Clinical diagnosis, can send toxicology screen to exclude ingestions
LP if atypical features, consider neuroimaging
Treatment is supportive, usually completely resolves within 2-3 weeks
Defect in ATM gene?
Ataxia telangiectasia
- AR disorder
- ATM gene involved in DNA repair
Presentation of ataxia telangiectasia?
Normal as infants
By age 2-3 develops ataxia, progresses to wheelchair bound by 15 years
Oculomotor apraxia: cannot make fast eye movements therefore turns head
Other features - telangiectasias, immunodeficiency (low Ig and T cell dysfunction), malignancy, pulmonary disease)
Investigations and treatment of ataxia telangiectasia
Serum AFP elevated
Serum IgA low
Genetic testing for ATM gene
Treatment is supportive, median age of death in mid-20s
Overview of Friedreich ataxia
Most common hereditary ataxia, AR or sporadic
Loss of function mutations in frataxin gene, usually due to expansion of a GAA-trinucleotide repeat
Causes atrophy of spinal cord and medulla
Clinical presentation of Friedreich ataxia
Presents in adolescence with progressive ataxia
Dysarthria
Sensory loss - particularly vibration and proprioception (posterior columns, dorsal root and peripheral nerves affected)
Eventual loss of DTRs
Systemic - hypertrophic cardiomyopathy, kyphoscoliosis, DM
Investigation and management of Friedreich ataxia
Neuroimaging of brain and spinal cord to exclude other causes, genetic testing
Treatment is supportive
Usually confined to wheelchair by late teens, age of death is usually mid-30s (cardiac complications)
Spina bifida occulta overview
Spinal cord dysraphisms
Failure of spinous processes to completely form or fuse
Spinal canal and overlying skin intact, may have tuft of hair or dimple
Very common (10% of population)
Usually no neurological consequence
All other types of dysraphisms have elevated AFP on screening
Protrusion of meninges through a spinal defect?
= meningocele
- looks like a cyst over (typically) lumbar spine
- spinal cord usually remains intact
- most patients asymptomatic neurologically
Protrusion of meninges and spinal roots through defect?
= myelomeningocele
- results in severe neurological complications with variable loss of function below the spinal level of the defect
- strength and sensation usually more affected than urinary and sexual function (although all are typically involved)
Protrusion of meninges and spinal roots through defect with an open lesion over the back?
= myeloschisis
- most severe form of spinal cord dysraphism
- direct communication between spinal canal and external environment
- high risk of CNS infection
Complications of myelomeningocele and myeloschisis?
Chiari II malformations
Cognitive issues (agenesis of corpus callous, ADHD)
Latex allergy (up to 70%)
Tethered cord (subacute gait abnormalities and urinary changes, usually during periods of growth)
Encephalocele
= defect of skull closure
May be bone only defect, or may have herniation of brain contents
Most frequently anterior or posterior
Anencephaly
= failure of the brain, skull and scalp formation
Majority result in spontaneous abortion or die during bith
No treatment available
Focal cortical dysplasia
Malformation of cortical development: isolated region(s) where neurons fail to segregate appropriately into six layers
Usually frontal, but can be anywhere
MRI: loss of grey-white differentiation, a “tail” of T2 hyper intensity from cortex to lateral ventricle
Typically presents with epilepsy, usually refractory to medical therapy (may need surgery)
More numerous/smaller gyri, resulting in a “cobblestone” appearance of the cortex
= polymicrogyria
May be focal or more diverse, can be congenital or due to prenatal CNS infection’Variable severity: mild neurologic deficits to severe ID, CP, epilepsy
Treatments target symptoms
“Double cortex”
= subcortical band heterotopia - some neurons appropriately migrate to cortex, others fail, resulting in two layers of neurons on imaging often with malformed cortex
More common in girls
Presents almost always with severe neurologic impairment
“Smooth brain”
= lissencephaly
- failure to form typical gyri and sulk
- may be primarily frontal, occipital or diffuse
- presents nearly always with severe neurologic impairment
Agenesis of the corpus callosum
Disorder of midline structure formation
Varies from dysgenesis (corpus callosum present but abnormal), to partial agenesis (missing either anterior or posterior portion only) to complete agenesis
Many causes, presentations vary
May have normal IQ with subtle cognitive impairments
Septo-optic dysplasia
Disorder of midline structure formation
Triad of absence of septum pellucidum, optic nerve hypoplasia and pituitary dysfunction
Can have normal cognition (but about 50% have mild to moderate ID)
Presentation of septo-optic dysplasia
Variable presentation
Can be discovered during neonatal period (poor transition, hypotonia), infancy (delayed visual milestones, congenital nystagmus, CP) or later (endocrine dysfunction, especially growth hormone deficiency)
Needs screening of pituitary function if imaging is concerning for optic nerve and corpus callosum development
Holoprosencephaly
Most severe form is lobar, includes single eye (cyclopean) and absent/misplaced nose (proboscis)
Semilobar = partial fusion of hemispheres
Lobar = partial interdigitation of hemispheres (usually frontally)
Severity is variable depending on extent of fusion but generally severe ID, CP and epilepsy
Disorders of posterior fossa formation
Dandy-Walker malformation
Joubert syndrome
Pontocerebellar hypoplasia
Dandy-Walker malformation
Enlarged fourth ventricle, elevated torculum, agenesis of cerebellar vermis, and typically agenesis of much of the cerebellar hemispheres
- usually have midbrain and pons malformation and hydrocephalus
- have fine motor and gait impairment with variable ID
“Molar tooth” appearance of midbrain on MRI?
Joubert syndrome
- disorder of posterior fossa formation
- severe developmental outcome with variable cranial nerve and bulbar symptoms
Pontocerebellar hypoplasia
Underdevelopment of brainstem and cerebellum
Multiple genetic causes
Universally poor neurological outcomes
Chiari malformation type I
Herniation of cerebellar tonsils through foramen magnum >5mm
- apparent obstruction of flow of CSF
- congenital or acquired
- acquired usually due to trauma or connective tissue disorders
- symptoms usually due to obstruction of CSF flow/impingement of posterior fossa structures
Symptoms of Chiari malformation type I
Symptoms usually due to obstruction of CSF flow/impingement of posterior fossa structures
- headaches are WORSE with Valsalva
- dysarthria, difficulty swallowing, ataxia
- majority are likely asymptomatic
Enlargement of central canal of spinal cord?
= Syringomyelia
- causes sensory loss and weakness in bilateral upper extremities and shoulder in a “cape like” distribution
- scoliosis, tethered cord
Chiari malformation type II
Associated with myelomeningocele
Associated with hydrocephalus and cognitive impairment (c/w type I)
Radiographically unique c/w type 1: fourth ventricle herniates through foramen magnum, “beaked” tectum, “kinked” medulla
Chiari malformation type III
Most rare form of Chiari malformation
Resembles type II on imaging
Associated with occipital encephalocele or cervical spinal dysraphism
Moyamoya disease
Narrowing of the distal internal carotid artery or MCA with the appearance of compensatory collateral vessels (“puff of smoke” on imaging)
RF: sickle cell disease, NF1, T21, history of radiation
Arterial ischaemic stroke
55% of paediatric strokes
Can be localised or thromboembolic
Localised arterial ischaemic stroke
Hypercoagulable state, response to endothelial damage, arterial dissection, inflammation and vasculopathy
Arteriopathy found in half of all cases
Sickle cell is one of the most common risk factors (ischaemic stroke in 11% of SCD patients by 20 years)
May cause microvascular occlusion
Thromboembolic arterial ischaemic stroke
Embolus from a distant site that travels to a cerebral artery
Cardiac disease is second most common risk factor (intracardiac thrombi or embolisms via R-L shunts)
Prothrombotic conditions: 13% of patients have a hereditary thrombophilia
Vasculitis and arterial dissection
Haemorrhagic stroke
May be intraparenchymal or subarachnoid
RF: vascular anomalies or hemorrhagic conversion after ischaemic stroke
- vascular anomalies account for 45% of non traumatic hemorrhagic strokes in children
Cerebral sinovenous thrombosis
Obstruction by clot of a major venous sinus draining the brain parenchyma, leading to infarct
May lead to secondary haemorrhage
40% occur in the neonatal period
Clinical presentation of stroke
Sudden onset focal neurological deficits occur in 85%
- anterior circulation (MCA or anterior cerebral artery): lateralised motor deficits, speech disturbance or fixed gaze deviation
- posterior circulation: altered mental status, dizziness, vomiting, ataxia, eye movement abnormalities
60% have signs which are not easily localised to a single vessel, seizure is the presenting feature in 30%
Mimics of acute ischaemic stroke
MELAS (mitochondrial encephalopathy, lactic acidosis and stroke-like episodes)
Migraine with aura
Seizure (with Todd paralysis)
Tumour
Metabolic derangement
Pseudotumour cerebri
Demyelinating disease
Infection
Somatoform disorder
Treatment of acute ischaemic stroke
Consider thrombolytic or endovascular treatment
PICU admission for neuroprotection
Start aspirin, consider anticoagulation in arterial dissection or CSVT
Extensive workup to exclude underlying thrombotic cause
Echo with bubble study
Neuroprotective care
- maximise cerebral perfusion and oxygenation: avoid hypotension, keep bed flat with head midline
- minimise metabolic demands: maintain normothermia, normal Na, and euglycaemia, provide seizure precautions and treat seizures aggressively
- start aspirin
- consider anticoagulation in arterial dissection or CSVT
- patients with SCD may require urgent exchange transfusion
Treatment of hemorrhagic stroke
Acute neurosurgical evaluation
Seizure prophylaxis
Monitor for signs of raised ICP and manage appropriately
Treat cause of bleed (as high risk of rebreed)
Treatment of Moyamoya
Consult neurosurgical team
Consider revascularisation surgery when appropriate
Overview of neonatal stroke
Defined as stroke between 20 weeks gestation and 28 days post birth
80% ischaemic, 20% haemorrhage or CSVT
Major RF: congenital heart disease, meningitis
Many RF that lead to hypercoagulability
Can co-occur with HIE
Presentation of neonatal stroke
Seizure at 24-72 hours of life (70-90% present with seizures)
Encephalopathy - irritable, lethargic with poor feeding
May develop early hand preference or delayed motor milestones
Investigation of neonatal stroke
MRI with vessel imaging is ideal
Echocardiogram with bubble study
Thrombophilia evaluation
Treatment of neonatal stroke
Anticoagulation is indicated only in CSVT that propagates or in some cases of cardiac disease
Seizure prevention
Prevention of stroke recurrence
Mechanism of ischaemia in cerebral sinovenous thrombosis
Thrombosis in the venous system results in outflow obstruction, venous congestion and increase in hydrostatic pressure - ultimately compromises arterial flow, leading to ischaemia
Clinical presentation of CSVT
Seizures most commonly
Focal/diffuse signs in older infants/children
Can have nonspecific features: headache, nausea, vomiting, impaired mental status, vision changes, hemiparesis, ataxia, CN palsies, sensory changes
Risk factors for CSVT
95% have a predisposing comorbid condition
RF = dehydration, infection, head injury, anaemia, autoimmune disorders, renal disease, cardiac disease, medications (steroids, oral contraceptives), metabolic conditions (DKA, homocystinuria)
Investigation of CSVT
CT or MRI
- CT with contrast but without dedicated venous imaging may miss diagnosis in up to 40% of cases
Think about predisposing condition, including infection and prothrombotic conditions
Treatment of CSVT
Supportive - monitor for raised ICP, consider EEG if unconscious
Rehydration and treatment of underlying cause
If neurologically stable, consider heparin, clean or warfarin
If unstable, consider neurosurgical evaluation
Arteriovenous malformation (AVM)
Abnormal arteries connect directly to draining veins without a capillary bed
Vein of Galen malformation
Dilation of the vein of Galen secondary to a mass of dilated vessels and an enlarged artery or AV fistula connected directly to the vein
Genetic conditions associated with cerebral aneurysms?
Aortic coarctation
Polycystic kidney disease
Sickle cell disease
Ehlers-Danlos type IV
Fibromuscular dysplasia
Clinical presentation of vascular anomalies
Seizures, headache, focal neurological deficits or haemorrhage
Haemorrhage risk for a known AVM is 2-4% per year
Vein of Galen malformation may present in infancy with high output heart failure and hydrocephalus
Investigation of suspected vascular anomaly?
MRI and MRA, CTA, or conventional angiogram
Consider underlying genetic condition
Treatment of vascular anomalies
Monitoring, with intervention based on risk/benefits
- may consider embolisation, surgical resection or radiosurgery
Overview of MS
Chronic, autoimmune, inflammatory, demyelinating disease of the CNS
Two types based on clinical course: relapsing-remitting MS or primary progressive MS
- paediatric cases are almost always relapsing-remitting at first
Clinical presentation of MS
First episode may be any neurological symptom without encephalopathy, and may include vision change, focal weakness, focal sensory change, ataxia etc
Usually begins between 2nd-4th decade (average age of paediatric MS onset is 15 years)
First attack in <18 years is only 2-5% of all MS patients
Diagnostic criteria for MS
2 or more non-encephalopathic clinical events with presumed inflammatory cause (separated by more than 30 days), OR
One clinical event plus MRI findings establishing demyelinating events, OR
First event not matching ADEM with MRI findings matching revised McDonald criteria (in children >12 years), OR
ADEM with recurrent event at least 3 months later without encephalopathy and with new lesions on MRI
Revised McDonald criteria in MS
MRI findings with at least one T2 change in two of four typical regions for MS (periventricular, juxtacortical, infratentorial, spinal cord)
Clinically isolated syndrome (CIS)
Single demyelinating event without evidence of dissemination in time or dissemination in space
Increased risk of developing MS
Presents with encephalopathy in 15-20%, and may be difficult to distinguish from ADEM
CSF features in MS
May have oligoclonal bands, elevated IgG index or pleocytosis
- note: CSF is not necessary for diagnosis of MS but may be helpful to rule out other disorders
Treatment of MS
Consider immunomodulatory therapy
Treatment of relapses - high dose steroids for 3-5 days, IVIG, plasmapheresis
Additional therapies - Vitamin D, symptom management, physical therapy as needed
Causes of drug-induced parkinsonism
Most common cause of hypokinetic movement disorder
Neuroleptic medications (dopamine antagonists)
Calcium channel blockers
Antiemetics (metoclopramide)
Examples of hypokinetic movement disorders
Parkinsonism (very rare in children)
Drug-induced parkinsonism (most common cause)
Infectious and autoimmune encephalitis
Primary Parkinsons (juvenile if onset <20 years): typically due to single gene mutations, loss of dopaminergic neurons from the substantia nigra
Neurodegenerative disease: including mitochondrial disorders, Wilson disease, or lysosomal storage disease, may have parkinsonism
Features of Parkinsonism
Acute onset to subacute onset after starting a new medication
Reduced amplitude and speed of movements
May have more frequent falls
Dystonia
Defined as concurrent activation of agnostic and antagonist muscle groups, resulting in abnormal twisting and posturing movements
Can be acute (secondary to dopamine antagonists) or chronic
Chronic dystonias
Primary: 12 types diagnosed by causative gene mutation (DYT1-12) as well as dopamine responsive dystonia, usually onset in adolescence
Secondary: with CP most commonly, usually have damage to basal ganglia, can also be seen with neurodegenerative disease
Features of acute dystonia
Typically focal, with cervical dystonia, blepharospasm, opisthotonus, tongue, trunk, extremity spasms or laryngospasms
Treatment of acute dystonia
Antihistamines, anticholinergics, benzodiazepines
Treatment of chronic dystonia
Botulinum toxin injections
Baclofen or trihexyphenidyl
Deep brain stimulation
Dopamine (for dopamine-responsive dystonia)
Chorea
Near-continuous irregular movements of a dancelike or writhing quality, neither rhythmic nor sterotyped
Athetosis
The same as chorea, but higher amplitude
Causes of chorea/athetosis
Often occurs with CP with basal ganglia injury co-occurring with dystonia
Physiologic chorea occurs at 6 months in healthy children
Juvenile Huntington’s disease
Metabolic causes - sugar, sodium, hypocalcaemia, or hyperthyroidism, can occur after cardiopulmonary bypass (postpump chorea)
Juvenile Huntington’s disease
AD neurodegenerative disease due to CAG repeat expansion in huntingtin gene on chromosome 4
The longer repeat, the earlier the onset of disease, normal is 20 repeats and juvenile onset seen with >80 repeats
Presentation of Sydenham chorea
Molecular mimicry with antistreptolysin O (ASO) antibodies cross-reacting with basal ganglia antigens
Develops 1-2 months after infection
Typically bilateral
Can occur with facial dystonia, hypotonia, dysarthria, milkmaid grip
Emotional lability and some OCD behaviours
Recurs in 20% of patients within 2 years
Associated with rheumatic cardiac and arthritis
Presentation of Huntington chorea
Very rare in children
Presents with rigidity, speech disorder, seizures and cerebellar signs
Family history with 90% paternal inheritance, may experience anticipation
ASO titers in Sydenham chorea?
Usually back to normal by the time chorea presents
Treatment of Sydenham chorea
IVIG, steroids
May need prophylaxis for rheumatic fever
Responds best to tetrabenazine (but only available in Huntington chorea)
Hypnagogic hallucinations
Vivid visual and auditory hallucinations occurring during the transition from wakefulness to sleep
