Neurology Flashcards
What percentage of patients with first unprovoked seizure have another seizure?
40%
80%-if 2 unprovoked seizures
In what age group are febrile seizures most common?
6 months to 60 months
What is the definition of a simple febrile seizure?
No focality <15 minutes Not recurrent in 24 hours Normal development Normal exam
What is the risk of developing epilepsy with febrile seizure?
2%
2X baseline risk if simple FS (0.5-1% doubles to 1-2%)
What is the likelihood of having another febrile seizure after the first one?
Overall 30%
BUT varies by age!
<1 year-50%
>1 year-20%
List 3 risk factors for recurrence of febrile seizures
Age <1 year Short duration of fever before seizure< 24 hr Low Fever 38-39 Family history of febrile seizures in 1st degree relative Young age at onset Male Attendance at daycare Complex febrile seizure
List 3 epilepsy syndromes that can be present with febrile seizures
Generalized epilepsy with febrile seizures
Severe myoclonic epilepsy of infancy (Dravet)
Temporal lobe epilepsy
When should you LP for febrile seizure?
<6 months for sure, some would say also <12 months
Components of counseling for febrile seizure
1) Reassurance
2) Seizure safety
3) Risk of recurrence/epilpesy
4) Anti-pyretics don’t reduce risk of FS
List 4 indications for MRI in first presentation seizure
Developmental delay Abnormalities on exam Focal seizures EEG abnormalities Age < 1 year
Describe the semiology of benign rolandic epilepsy
Facial movement common Facial numbness Twitching Guttural vocalizations Drooling Dysphasia and speech arrest UE >LE movements more common Most happen at night or on awakening ,
What is the age of onset of benign rolandic epilepsy?
Age of onset 3-13 years
Peak incidence between 7-9 years
Resolves by adolescence
What is the characteristic EEG finding in
Broad-based centrotemporal spikes increased in frequency during drowsiness and sleep
Describe the semiology of benign epilepsy with occipital spikes (Panayiotopoulos)
Autonomic features
Vomiting
Syncope-like seizures, with sudden loss of muscle tone and unresponsiveness, pallor, miosis, incontinence, coughing, and hypersalivation
USUALLY AT NIGHT
What is the prognosis of Benign epilepsy with occipital spikes ?
Spontaneous remission usually occurs within 2-3 years from onset
Which epilepsy syndrome is often preceded by febrile seizures where patients have atrophy and gliosis of hippocampus/amygdala?
Temporal lobe epilepsy
What is the most common cause of surgically remediable epilepsy?
Temporal lobe epilepsy
What is the classic EEG finding in Landau Kleffner?
Electrical status epilepticus during sleep->85% of non-REM sleep
List 3 clinical features of Landau Kleffner
Loss in language function beginning age 3-6
Auditory verbal agnosia (behave as if they are deaf)
Expressive language deficits
Personality disorders
Hyperkinetic behaviour
Preservation of overall cognitive function
List 3 clinical features of Rasmussen encephalitis
Unilateral intractable partial seizures
Epilepsia partialis continua
Progressive hemiparesis of the affected side
Progressive atrophy of the contralateral hemisphere
What is the typical age of onset of absence seizures?
5-8 years of age
Describe the semiology of absence seizures
No aura
Last for only a few seconds
Flutter or upward rolling of the eyes
Simple automatisms like lip-smacking or picking at clothing
What is the classic EEG finding in absence seizures?
3 Hz spike–and–slow wave discharges
What is the prognosis of absence seizures?
Most outgrow by adulthood
Small group will develop JME
Describe the clinical features of benign myoclonic epilepsy of infancy
Onset of myoclonic and other seizures during the 1st yr of life
What is the age of onset of juvenile myoclonic epilepsy?
Starts in early adolescence (average 15 years)
What are the 3 seizures types seen in juvenile myoclonic epilepsy?
Myoclonus (usually early morning, first sign)
GTC
Juvenile absence
List 3 triggers for seizures in juvenile myoclonic epilepsy?
Sleep deprivation
Alcohol
Photic sitmulation
Gognitive acitvites
What is the characteristic EEG finding in juvenile myoclonic epilepsy?
Generalized 4-5 Hz polyspike–and–slow wave discharges
What is the prognosis of juvenile myoclonic epilepsy?
Life long AEDs
List 2 treatment options for juvenile myoclonic epilepsy
Valproate
Lamotrigine
(Similar to absence seizure tx)
At what age and how does Dravet syndrome typically present?
Begins with focal febrile status epilepticus in 1st year of life (6 months)
List 2 clinical features of Dravet syndrome
1) Refractory epilepsy-often requires KD or vagal nerve stimulation
2) Neurodevelopmental problems beginning in infancy
Describe the semiology of infantile spasms
Spasms of neck, trunk, and extremities
Followed by a tonic phase ~10 seconds
Usually symmetric, often occur in clusters, particularly in drowsiness or upon arousal
How do you differentiate benign myoclonus of infancy (different from benign myoclonic epilepsy of infancy!) from IS?
Only when asleep
Normal EEG
Normal development
What is the age of onset and resolution of benign myoclonus of infancy?
3-8 months of age
Increase in intensity and severity over weeks or months and then remit spontaneously at 2-3 years of age
When is the typical age of presentation of infantile spasms?
Present between 3-7 months of age; onset after 18 months is rare
When do infantile spasms typically resolve?
Age 3-4 years
But usually other seizure types emerge….
What is the characteristic EEG finding in infantile spasms?
Hypsarrhythmia (high-voltage, slow, chaotic background with multifocal spikes)
List 5 conditions associated with infantile spasms
Tuberous sclerosis (10%) Cortical dysplasias Miller-Dieker syndrome Aicardi syndrome Hemimegancephaly Chromosome abnormalities NF1 IEM Congenital infections Perinatal insults
What is west syndrme?
Infantile spasms with DEVELOPMENTAL REGRESSION
What epilepsy syndromes typically evolve into Lennox Gastaut?
Many patients start Ohtahara→ West syndrome →Lennox-Gastaut
What is the typical age of patients with Lennox Gastaut?
Age of 2 – 10
What is the semiology of Lennox Gastaut?
Multiple seizure types:atypical absences, myoclonic, astatic, and tonic seizures
Does Lennox Gastaut lead to developmental delay?
YES
Poor outcome
List 5 epilepsy syndromes of infancy
1) Benign familial infantile epilepsy
2) Benign focal epilepsies in infancy
3) Genetic epilepsy with febrile seizures plus
4) Myoclonic epilepsy of infancy
- Dravet syndrome
5) Infantile spasms
6) Benign idiopathic neonatal seizures
What is the typical clinical presentation of benign idiopathic neonatal seizures?
Usually apneic and unifocal clonic seizures that start around the fifth day of life (unlike GTC in benign familial neonatal seizures)
What is the characteristic EEG finding in benign idiopathic neonatal seizures?
Interictal EEG shows a distinctive pattern called theta pointu alternant (runs sharp 4-7 Hz activity)
Ictal EEG shows multifocal electrographic seizures
When do benign idiopathic neonatal seizures usually resolve?
By 6 weeks
Good prognosis!
What is the characteristic EEG finding in benign familial neonatal seizures?
Interictal EEG is normal
How are benign familial neonatal seizures inherited?
Autosomal dominant
Mutations in KCNQ2 and KCNQ3 genes
What are the important components of seizure education?
Supervised swimming
Helmet
Driving
Seizure safety
What AEDs can you use for absence seizures?
Ethosuximide, valproate, lamotrigine
What AEDs can you use for focal seizures?
Carbamazepine, keppra, topiramate
What AEDs can you use for generalized seizures in children >2 years of age?
Valproate, keppra, topiramate
What AEDs can you use for JME?
Valproate, lamotrigine
What AEDs can you use for infantile spasms?
Vigabatrin
ACTH
When should you NOT use valproate?
If metabolic disorder has not been ruled out
<2 years of age
When should you NOT use carbamezipine or phenytoin?
Absence or myoclonic
In general, after how many years of being seizure free should AEDs be discontinued?
2 years
Side effects of valproic acid
Transaminitis Pancreatitis Thrombocytopenia Weight gain Hair loss Tremor PCOS Teratogenic
Side effects of phenytoin
Gingival hyperplasia Hirsutism Decreased bone mineral density SJS Folic acid depletion
Side effects of keppra
Behavioural disturbance
Side effects of lamotrigine
SJS
Side effects of vigabatrin
Retinal toxicity
Concentric visual loss
Side effects of topamax
Kidney stones
Cognitive slowing
Weight loss
Side effects of ethosuximide
Agranulocytosis
List 10 differentials for seizures
Apnea Breath holding spells Hyperekplexia Compulsive Valsalva Vasovagal syncope Orthostatic hypotension Familial hemiplegic migraine BPPV Cyclic vomiting syndrome Stereotypies/tics Panic/anxiety attacks Long QT Alice in Wonderland syndrome Migraines-confusional
List 10 differentials for seizures
Apnea Breath holding spells Hyperekplexia Compulsive Valsalva Vasovagal syncope Orthostatic hypotension Familial hemiplegic migraine BPPV Cyclic vomiting syndrome Stereotypies/tics Panic/anxiety attacks Long QT Alice in Wonderland syndrome Migraines-confusional Psychogenic non-epileptiform seizures Masturbation/self stimulating behaviour
What is the typical age of presentation of breatholding spells?
6 and 18 mo of age
What clinical clues suggest a diagnosis of breatholding spells?
Provoked with injury, anger, and frustration, particularly with surprise
Starts with cry, then apnea, cyanosis–>can lead to syncope or anoxic seizure
List 3 steps in management of breatholding spells
Reassure parents-outgrow within a few years, almost all by 8 years
Parent CPR
Consistent discipline, do not positively reinforce, give child warning before trigger onset as surprise makes worse
Preparation rather than surprising
Iron supplementation if iron deficient
What is the main reason diazepam is not used as an anticonvulsant in neonates?
Neonates have decreased liver metabolism of diazepam
Can accumulate with repeated use and cause increased toxicity
What is the clinical signs of infantile masturbation?
May occur in girls 2-3 yr of age
Perspiration, irregular breathing, and grunting, but no loss of consciousness
What sutures are fused in scaphocephaly?
Sagittal suture
No hydrocephalus!
What sutures are fused in plagiocephaly?
Unilateral coronal or lambdoidal synostosis
What sutures are fused in trigonocephaly?
Metopic suture
What sutures are fused in kleeblattschädel?
Multiple sutures fuse prematurely
What sutures are fused in acrocephaly?
Sagittal, coronal, and lambdoid synostosis
Name 2 complications of craniosynostosis
Raised ICP (if two or more sutures are fused) Cognitive/neurdovelopment deficits due to inhibition of brain growth Poor self esteem and social isolation due to the abnormal appearance
When is the optimal timing of craniosynostosis surgery?
8 to 12 months of age
List 4 physical exam findings that would be contraindications to a LP
Cushing triad
Absence of reactive pupils, Loss of brainstem reflexes, decorticate/decerebrate posturing
Infection at site of LP
Myelomeningocole
Petechial Rash
List 4 contraindications to LP
Suspected mass lesion of the brain causing shift of the midline
Suspected mass lesion of the spinal cord
Symptoms and signs of impending cerebral herniation
Critical illness (on rare occasions)
Skin infection at the site
Thrombocytopenia with a platelet count <20 × 109/L
What patients are at highest risk for chronic valproic acid toxicity?
<2 years old Organic brain disease Developmental delay of unknown etiology Metabolic disorders Multiple AEDs
List 4 clinical features of acute valproic acid toxicity
Vital signs – Respiratory depression, hypotension, tachycardia, hyperthermia
Metabolic – Hyperammonemia, anion gap metabolic acidosis, hyperosmolality, hypernatremia, hypocalcemia
Gastrointestinal – Nausea, vomiting, diarrhea, mild toxic hepatitis
CNS Mild-moderate lethargy, coma, cerebral edema
Miosis, agitation, tremors, myoclonus
Rare – fever, heart block, pancreatitis, ARF, pancytopenia, seizures, ARDS
List 4 clinical features of chronic VPA toxicity
Hepatic failure Hyperammonemia Pancreatitis Alopecia Leukopenia Thrombocytopenia Anemia Cerebral edema
What 4 investigations would you order in suspected chronic VPA toxicity?
- VPA level (therapeutic serum 50 to 100 mg/L (350 to 700 µmol/L) )
- Ammonia (hepatotoxicity does not always occur with hyperammonenmia)
- Liver function, AST, ALT, lipase, amylase
- CBC
- Carnitine level
What are the most common types of headaches in children?
1) Migraine
2) Tension
List 3 characteristics of tension headaches
Mild to moderate in severity
Diffuse
Not affected by activity
Nonthrobbing (often described as a constant pressure)
Duration 30 min to 7 days
What is the best pharmacologic management of tension headaches?
Ibuprofen > acetaminophen
How much analgesic use does it require to develop medication overuse headaches?
Patient taking analgesics >15days /month for >3months
How do you treat medication overuse headaches?
Withdraw slowly, can give steroids as transition for abrupt withdrawl
Definition of idiopathic intracranial hypertension
Inc ICP with normal head imaging
List 4 risk factors for idiopathic intracranial hypertension
Obesity Female Systemic disease (SLE, hypo/hyperthyroidism) Rapid changes in weight OCP Tetracycline TCAs Growth Hormone Accutane/Retinoids
What complication can result from untreated idiopathic intracranial hypertension?
Permanent visual field loss
What is the treatment of idiopathic intracranial hypertension?
Acetazolomide
Weight loss
Cessation of triggering med
List the ILAR diagnostic criteria of migraines
Diagnosis requires:
- 5 attacks
- 4-72 hours each
2 of:
- Moderate to severe in intensity
- Unilateral (although commonly B/L in children)
- Pulsating
- Worse with activity
1 of:
- Nausea OR Vomiting
- Photophobia ANDphonophobia
NOT ATTRIBUTABLE TO ANOTHER DISORDER
What conditions on family history are often associated with migraines?
Migraines
Cyclic vomiting
Motion sickness
Menstrual headaches
List 5 triggers for migraines
Poor sleep
Dehydration
Weather changes
Food no longer considered a common trigger
Menses
List 3 types of migraine auras
Visual (most common)
-photopsia (flashes of light)
Sensory
- Bugs crawling
- Numbness
Dysphasic
-Difficulty or inability to verbally respond
Hemiplegic
Basilar
List 3 clinical features of confusional migraines
Agitation, disorientation, aphasia
Eventually turn into typical migraines
List 3 clinical features of abdominal migraine
Dull pain, moderate to severe, from 1h – 72h, usually midline
Must have at least 2 of →anorexia, nausea, vomiting, or pallor
Describe Alice in Wonderland Syndrome
Visual hallucinations
Perceptual distortions
Impairment of time sense
Child isn’t scared and can describe the experience
Perceptual disturbance lasts days to months, recover spontaneously
Indications for migraine prophylaxis
Headache is frequent (≥1/week)
Affecting school/life
List 3 options for abortive treatment of migraines
Fluids/hydration
NSAIDs (should not use more than 2-3x/week)
Triptans (>12 years)
Antiemetics (prochlorperazine, metoclopramide) -on top of NSAID/triptan
List 3 options for prophylaxis of migraines
Riboflavin/Mg/CoQ10 CCBs Amitriptyline VPA Topiramate Gabapentin Propranolol Prochlorperazine
Which migraine prophylaxis to avoid in asthma
Propanolol
List 5 features of basilar migraine
Vertigo, tinnitus, diplopia, blurry vision, scotoma, ataxia, occipital h/a
List 4 migraine variant conditions
Paroxysmal vertigo
Cyclic vomiting syndrome
Abdominal migraine
Others:
Alice in Wonderland syndrome
Retinal migraine
Basilar migraine-NO TRIPTANS
List 5 hyperkinetic movement disorders in childhood
Stereotypies Tics Chorea Ballism Dystonia Athetosis Tremor Myoclonus
Differential diagnosis for ataxia
Acute cerebellar ataxia
Guillain Barre
Labyrninthitis
Migraine syndromes (e.g. basilar)
Post traumatic
Tumours
ICH
Stroke
ADEM
Encephalitis/abscess
Conversion disorder
Congenital malformatoins of posterior fossa (e.g. Dandy walker, joubert, chiari)
Metabolic disorders ( Abetalipoproteinemia, arginosuccinicaciduria, Hartnup disease)
Degenerative (e.g. AT, friedrich ataxia, spinocerebellar ataxia)
List 5 clinical features of ataxia telengeactasia
Ataxia (usually begins at age 2)
Visual disturbance (saccade pursuit, strabismus, nystagmus, oculomotor apraxia of horizontal gaze)
Telangiectasiaes (mid chilhood)
Immunodeficiency (low IgA, IgG, IgE)
Increased risk of malignancy (leukemia, lymphoma, brain tumours)
How is ataxia telangiectasie inherited?
AR
List 3 clinical features of Friedrich ataxia
Ataxia (after AT, but before 10 years)
Explosive dysarthric speech
Skeletal abnormalities (pes cavus, hammertoes, kyphoscoliosis)
Hypertrophic cardiomyopathy
What medications are recommended in Friedrich ataxia
Antioxidant therapy with coenzyme Q10 and vitamin E
What is the difference between chorea and athetosis?
Chorea-rapid, chaotic movements flowing from one body part to another
Athetosis-slow, continuous, writhing movements that repeatedly involve the same body part(s)
List 3 clinical features in keeping with chorea
Motor impersistence, with difficulty keeping the tongue protruded (“darting tongue”) or maintaining grip (“milkmaid grip)
Occurs at rest and with action
Increases with stress
Disappears in sleep
Differential diagnosis of chorea
1) Genetic
- Huntington Disease
- Ataxia Telangiectasia
- Wilson
- Benign Hereditary Chorea
- Spinocerebellar Ataxia
2) Basal-Ganglia Lesions
- Tumours
- MS plaques
- Stroke lesions
3) Para-Infections/Autoimmune
- Sydenham chorea
- SLE
- Antiphospholipid Antibody Syndrome
- Post-infectious/Post-vaccine
- Paraneoplastic
- Chorea Gravidarum (pregnancy)
4) Infectious
- HIV
- Viral (Measles, Mumps, Varicella)
- Toxoplasmosis
- Endocarditis
- Neurosyphilis
- Lyme
5) Toxic/Metabolic
- Porphyria
- Hypo/hypernatremia, Hypocalcemia
- Hyperthyroid, Hypoparathyroid
- Liver/Renal failure
- Poisoning → CO, Mercury, Manganese, Organophosphate
6) Drugs
- Dopamine-drugs
- Antiepileptics, Psych meds
- Calcium channel blockers
- Lithium
- Steroids
- OCPs
List 3 clinical characteristics of Sydenham chorea
Chorea
Hypotonia
Emotional lability
How long after GAS does sydenham chorea typically present?
Occurs 1-8mo after GAS infection
What is the prognosis of sydenham chorea?
Usually spontaneously resolves in 6-9mo, but can persist
Differential for tremor
Essential tremor
Drugs-valproate, lithium, TCAs
Metabolic-hyperthyroidism, hypoglycemia, hypocalcemia
Peripheral neuropathy
Degenerative disease-Wilsons, huntington, fragile X premutation
Structural-stroke, cerebellar malforamtion, MS
Psychogenic
List 4 causes of dystonia
1) Primary Generalized Dystonia
E.g. Dopa-responsive dystonia → hallmark is diurnal variation
2) Drug-Induced Dystonia
- Antipsychotics and antiemetics that block dopamine
3) Cerebral Palsy-dyskinetic form
4) Metabolic Disorders
- e.g. Wilsons, glutaric aciduria, leigh syndrome, , niemann Pick Type C
How do you treat acute dystonic reaction?
IV Benadryl
IV Benzotropine
How long do you need to be on a medication to get tardive dyskinesia?
After at least 3 months of med use and may not resolve after med is discontinued
In what type of patients is dyskinetic CP more common?
Term with perinatal asyphyxia?
What is the prognosis of • benign paroxysmal torticollis of infancy (recurrent episodes of cervical dystonia starting at 1 y.o.)
Resolves by 3 y.o.
List 2 things that make tics worse and 2 things that make tics better
Worse:
Stress
Stimulant meds
Better:
Sleep
Relaxation
Concentration
List 3 methods to manage tics
Ignore
CBT
Meds only if the tics cause significant distress or impairment in functioning
(Clonidine, Guanfacine, Haldol, pimozide, SSRI if comorbid OCD/anxiety)
List the DSM V criteria for Tourettes
- 2 or more motor tics and at least 1 vocal tic
- Tics for at least a year
- The tics can occur many times a day (usually in bouts) nearly every day
- Begin before 18 years of age.
- Not consistent with another medical condition
Name 2 conditions associated with Tourette’s
OCD
ADHD
ODD
What pharmacologic treatment is recommended for Tourette’s?
Risperidone
What is PANDAS?
Neuropsychiatric disorders (OCD, tics, and Tourettes) for which a possible relationship with GAS infections has been suggested
List 3 things that support diagnosis of Tourettes in a child with tics?
Male (4:1)
Family history of tics
ADHD, OCD
List 10 conditions in the differential for stroke
Migraine Seizure Meningitis Demyelination Hypoglycemia IEM-e.g. MELAS Alternating hemiplegia Acute cerebellar ataxia Channelopathy
List 10 causes of acute ischemic stroke
Arteriopathic
- Moya Moya
- Vasculitis
- Focal cerebral arteriopathy
- PHACES
Cardiac
- Complex congenital heart diseases
- Arrhythmias
- Cardiomyopathy
- Endocarditis
Hematologic
- Iron deficiency
- Sickle Cell
- Coagulation disorders → factor V leiden, APA syndrome
- Prothrombotic meds → OCPs, asparaginase (chemo)
List 3 steps in the management of acute ischemic stroke
- Antithrombotics for secondary stroke prevention-heparin, ASA
- Neuroprotection
- Tight control of glucose, temp, seizures
- Maintain cerebral perfusion - Manage underlying disease
- Sickle cell – transfusion
- Vasculitis – immunosuppression
- Moyamoya – revascularization surgery - Rehabilitation
What is the most common cause of CP in term babies?
Perinatal stroke
List 2 complications of CSVT
Raised ICP
Optic neuropathy
Venous infarction
Cerebral edema
List 5 risk factors for CSVT
Prothrombotic conditions – factor V leiden, protein C/S deficiency, prothrombin mutation, antithrombin III deficiency, APA, pregnancy
Dehydration
Iron-deficiency anemia
Drugs/Toxins – OCPs, aspariginase
Systemic illness – sepsis, DIC
Chronic diseases – IBD, leukemia
Nephrotic syndrome
IEMs – homocystinuria
Trauma
Infection causing septic thrombophlebitis
Venous malformations
Compression – e.g. birth
Iatrogenic – neurosurgery, CVLs, ECMO
How do you treat CSVT?
Anticoagulation with unfractionated or low molecular weight heparin
Treat for 3 months, then re-image– if persistent thrombus, extend to 6 months
List 5 causes of hemorrhagic stroke
- Vascular malformations/disorders
- AVM
- Cavernomas (cavernous angiomas)
- Vein of Galen malformations
- Aneurysms (uncommon)
- Moyamoya
- Vasculitis
- Tumours with unstable vessels - Drugs/toxins (cocaine, amphetamines)
- Hematologic Disorders
- ITP
- HUS
- Liver disease/failure
- Vitamin K deficiency/Hemorrhagic disease of the newborn
- DIC - Trauma
List causes of acquired peripheral neuropathies in chidlren
- Infections
a. Lyme – rarely get peripheral neuropathy in children
b. Chagas (chronic)
c. Diphtheria
d. Leprosy
e. Rabies - Guillain-Barre Syndrome(Nelsons)
- Rheumatic Diseases
a. Churg-Strauss
b. HSP/IgA Vasculitis
c. IBD
d. JIA
e. PAN
f. Sarcoid
g. Sjogren
h. SLE
i. Wegener Granulomatosis - Organ Failure – e.g. uremia
- Other:
a. Diabetes
b. Hypothyroidism
c. Celiac
d. Porphyria
e. Malignancy - Medications
a. Antiretrovirals
b. Chemo agents
c. Phenytoin
d. Thalidomide - Vitamin Deficiency or Excess – particularly B-vitamins
- Toxins
a. Arsenic
b. Lead
c. Mercury
d. Glue
e. Organophosphates
List causes of hereditary neuropathy in children
- Charcot-Marie-Tooth
- Peroneal Muscular Atrophy
- Dejerine-Sotas
- Roussy-Levy
- Refsum Disease
- Fabry Disease
- Giant Axonal Neuropathy
- Congenital Hypomyelinating Neuropathy
- Leukodystrophies
What infectious agents are associated with Guillain Barre?
Campylobacter
H. pylori
Mycoplasma
West nile
List 2 signs of impending respiratory failure in Guillain Barre?
Bulbar involvement!
Dysphagia
Facial weakness
List 3 clinical features of Miller Fisher syndrome
External ophthalmoplegia
Ataxia
Muscle weakness with areflexia
What CSF findings are consistent with GBS?
High protein + normal WBC (diagnostic!), normal glucose
What investigations do you order in GBS?
MRI spine
NCS
EMG
List 3 steps in management of GBS
Admit on monitors
Monitor resp status with spirometry
If rapid progression – IVIg +/- plasmapheresis +/- immunosuppression
Gabapentin for chronic neuropathic pain
When should you expect a patient with GBS to recover?
2-3 weeks
List 3 poor prognostic factors in GBS
CN involvement
Intubation
++disability at presentation
What is the most common genetically determined neuropathy?
CMT
How is CMT inherited?
AD
Describe clinical features of CMT
Asymptomatic until late childhood
Clumsy
Muscle wasting
Stork-like legs
Footdrop
Enlarged palpable nerves
High-arched feet
Can also get sensory and autonomic involvement
Differential for facial nerve palsy
Congenital facial palsy-Moebius syndrome Bell's Palsy (HSV) AOM Lyme Ramsay Hunt Cholesteatoma Melkersson-Rosenthal syndrome ( facial paralysis, episodic facial swelling, and a fissured tongue) Sarcoidosis
Management of Bell’s palsy
Prednisone
Management of dry eyes
What is the prognosis of Bell’s palsy?
85% full recovery
10% mild residual weakness
5% severe residual weakness
What is Ramsay Hunt caused by?
Reactivation of VZV
List two causes of congenital facial palsy
Congenital absence of depressor angularisoris muscle
Moebius
What is the abnormality sif often associated with congenital absence of depressor angularisoris muscle ?
Cardiac
Describe the clinical features of complex regional pain syndrome
Pain out of proportion to history and physical findings
Pain and allodynia severe
Pain with movement of joint
Warm, erythema, edema initially, then cool/clammy
Disuse atrophy
Preceding history of trauma in many cases
Treatment of CRPS
PT/OT
Psychotherapy
Stop meds
For severe, refractory-pain reducing procedures (e.g. regional sympathetic nerve block)
Definition of concussion
Trauma-induced brain dysfunction without demonstrable structural injury on standard neuroimaging
List 5 clinical signs/symptoms of concussion
1. Symptoms/physical signs Headache Nausea/vomiting Dizziness Visual disturbances Photophobia Phonophobia Loss of consciousness
2. Behavioural changes Irritability Emotional lability Sadness Anxiety Inappropriate emotions
3. Cognitive impairment Slowed processing Difficulty concentrating/attention Impaired memory/learning Confusion
- Sleep disturbances
Sleeping more than usual
Sleeping less than usual
When can patients return to play?
Once symptom-free and back to full-time school attendance without accommodations, the student can start with graduated return to play
Should be symptoms free for 7-10 days
How long does each phase last in return to play protocol?
24 hours, go back if symptoms
List 3 preventive strategies to prevent concussion
Promote fair play and sportsmanship
Advocating for rule changing (ie) no hitting/check below the head
Helmets don’t prevent concussion, but reduce risk of severe brain injury
Return to learn protocol
- Cognitive rest
- Decrease and limit cognitive tasks and screen time at home. No school - Increase cognitive tasks
- As symptoms improve, slowly increase cognitive tasks at home in 15 min to 20 min increments. - Resume modified school attendance
- As symptoms continue to improve, resume school attendance. Start with half-days or only certain classes (avoid gym, music, shop). Limit homework assignments to 15 min to 20 min blocks. - Increase school attendance
- Gradually increase school attendance to full days as symptoms allow. Specific accommodations may be required to avoid symptom exacerbation. Tests should be limited to one per day in a quiet area, with unlimited time and frequent breaks
Return to play protocol
- No activity * (optimally 7-10days)
- Light aerobic exercise
-Walking, swimming or stationary cycling
No resistance training - Sport-specific exercise
- Simple drills - Noncontact training drills
- Complex drills - Full-contact practice
- Return to play
What advise would you give patients re: return to play?
No activity for at least 7 days.
Return to Learn prior to return to play
Return to play in step wise approach after 7 days rest, each step should take at least 24 hours.
6 steps – 6 days if all goes well.
No practices for 1 week, slow return
If in two weeks return has gone well, may play in games.
List 5 etiologies for CP
Antenatal factors-80% Prematurity Perinatal hypoxic-ischemic injury <10% Congenital abnormalities Genetic susceptibility Multiple births Stroke Intracranial hemorrhage Intrauterine infection Acquired postnatal causes (stroke, sepsis/meningitis, kernicterus
What is the most common cause of spastic diplegia?
Prematurity (20-34 weeks)
PVL
Rare: Urea cycle defects
What is the most common cause of spastic hemiplegia?
Stroke
What is the most common cause of dyskinetic CP?
Asphyxia
Kernicterus
Less common: mitochondrial disease, glutaricaciduria, Segawa disease (doparespsonisve)
List 5 early signs of CP
- Excessive docility or irritability
- Poor feeding
- Delay in the disappearance or exaggeration of a developmental reflex (>6 months)
- Rolling over early
- Persistent ATNR >7 months
- Delayed motor milestones
- Early hand preference (1 yea)
- Persistent extension of legs with vertical suspension
- Toe walking
- Delayed walking
List 3 clinical features of spastic hemiplegia
Decreased spontaneous movements on the affected side
Hand preference at a very early age (by 1 year)
Arm more than leg
Delayed walking, circumductive gait
List 3 clinical features of spastic diplegia
Bilateral spasticity of the legs ≥ arms Scissoring legs when suspended by axillae Commando crawl Diapering difficult (hip adduction) Unable to sit Bilateral ankle equinovarus Tiptoe walking
List 3 clinical features of spastic quadriplegia
All limbs impaired
High rate of cognitive delay and seizures.
Speech and vision highly affected
Swallowing difficulties → aspiration pneumonia
Gross Motor Function Classification System (GMFCS)
Level I – Walks without limitations
Level II – Walks with limitations
Level III – Walks using a hand-held mobility device (canes, crutches, and anterior and posterior walkers that do not support the trunk)
Level IV – Self-mobility with limitations; may use powered mobility
Level V – Transported in a manual wheelchair
What investigations to order in CP?
MRI Brain
Hearing and Vision screening
Consider genetic or metabolic as indicated
Inherited thrombophilic disorders should be tested if in utero stroke suspected
List the components of management of CP
OT, PT, SLP, Developmental peds Adaptive equipment Family and community resources Treatment of spasticity/contractures-tendon releases, benzos, baclofen, botox, casting etc. Psych for behaviour
When does the parachute reflex appear and disappear?
Appears at 7-9 months and does not disappear
When does moro reflex disappear?
6 months
When does grasp reflex disappear?
2 months
When does ATNR disappear?
7 months
List 5 features that are highly suggestive of GBS as unerlying cause of progressive weakness
- **Progression over days to a few weeks
- Relative symmetry
- Mild sensory loss
- Onset with extremity pain or discomfort
- Cranial nerve involvement
- Onset of recovery 2-4 weeks after halt of progression
- Autonomic dysfunction
- Initial absence of fever
- Elevated CSF protein after 1 week of symptoms
- Abnormal NCS with slowed conduction or prolonged F waves
List 5 features that work against the diagnosis of GBS as underlying cause of progressive weakness
Marked, persistent asymmetry of weakness
Persistent bladder or bowel dysfunction
Bladder or bowel dysfunction at onset
Mononuclear leukocytosis in CSF > 50/uL
Sharp sensory level
What investigations would you order in suspected GBS?
LP
NCS-reduced conduction within days of symptoms
EMG-denervation, usually need 2-3 weeks of symptoms
MRI spinal cord with Gad-r/o differential
List 3 severe complications to monitor in GBS
Bulbar dysfunction with aspiration risk
Respiratory failure
Autonomic dysfunction → arrhythmias, asystole
What is the pathophysiology of myasthenia gravis?
Ach-receptor-antibodies
Describe the clinical features of neonatal mysathenic syndrome
Infants born to myasthenic mothers
Placentally transferred anti-ACh receptor antibodies
Characterized by respiratory insufficiency (may need vent), inability to suck/swallow, generalized hypotenia
After the Ab resolve, regain normal strength (within a few weeks)
List 3 cliical features of juvenile myasthenic syndrome
Ptosis/EOM weakness are earliest and most constant signs
Pupillary responses preserved
Dysphagia/facial weakness also common (infant feeding difficulties, choking)
Poor head control with weakness of neck flexors common.
Weakness of limb-girdle muscles and distal muscles of the hands
DTRs diminished but not lost
No fasciculations, myalgias, or sensory symptoms
***Rapid fatigue of muscles is a distinguishing feature
What investigations would you order in suspected myasthenia gravis?
EMG: decremental response to repetitive nerve stim; responses diminish rapidly until muscle refractory to further stim
NCS: normal
Anti-Ach antibodies (only +ve in 30%)
Anti MuSK antiobodies
Serologic markers of autoimmune (ANA, c3/c4…);
Check thyroid
CK: normal
Treatment of myasthenia gravis
- Cholinesterase inhibitors: neostigmine, pyridostigmine
- Immunosupporession second line; PLEX may be used
- ?Thymectomy, might provide a cure
- Avoid certain drugs-gentamicin, succinylcholine
Clinical presentation of botulism
Honey/soil exposure (spores near construction, farm)
Descending paralysis
Initially bulbar palsies (ptosis, dysarthria, dysphonia, dysphagia→ facial weakness)
***Desceding paralysis over hours to days
Decreased DTRs
How do you diagnose botulism?
Stool +ve toxin
EMG: decreasing response with stimulation similar to MG
How do you treat botulism?
Botulism Ig or IVig is mainstay of Rx (within 72h)
Supportive care
Clinical features of tick paralysis
***Ascending paralysis (resembles GBS)
Absent DTRs
***Progresses over hours to days
Facial/ocular/lingual muscles may be involved
Sensory paresthesias can occur in face and extremities
Once tick removed, recover within hours-days.
What disease is highly associated with optic neuritis?
MS
Others:
NMO
ADEM
What are the clinical features of optic neuritis?
Monocular (sometimes binocular) vision loss
Eye pain
Develops over hours to days and peaks within 1-2 weeks
RAPD positive
Over what time period do most patients with optic neuritis recover?
Most patients with optic neuritis recover functional vision within one year.
What is the treatment of optic neuritis?
IV steroids in select patients
List 3 clinical features that would suggest transverse myelitis as a cause of weakness
Neck/back pain Bilateral sensorimotor chances Urinary retention occurs early Sensory levels Initially flaccidity, progresses to spasticity
What tests would you order in suspected transverse myelitis?
MRI with and without Gad-r/o mass lesion, enhancing lesion in spinal cord
LP after mass lesion ruled out (will show pleocytosis, high IgG index)
NMO antigen.
Describe the clinical features of NMO
Recurrent episodes optic neuritis and/or transverse myelitis
List 2 risk factors for NMO
F>M
Asian>black/white
List 3 differences between MS and NMO
In NMO:
(1) other parts of nervous system generally not involved
(2) recovery not as complete
(3) ON more frequently bilateral in NMO than in MS
(4) NMO is more frequently fatal than MS.
What CSF finding is characteristic of NMO?
↑ WBC (usually >50)
Nooligoclonal bands (unlike MS)
What is the definition of MS
Chronic demyelinating d/o of brain, SC and optic nerves
Relapsing-remitting course
Episodes separated in time and space
-Episodes >24 hr and separated by >30 days
OR
-Accumulation of T2/enhancing lesions over 3 month period
What is the typical age of presentation of ADEM?
5-8 years
Describe clinical features of ADEM
H/A Vomiting Fever Seizures Encephalopathy Multifocal neurologic deficits (: visual loss/ON, CN neuropathies, ataxia, motor deficits (TM or hemiparesis), bladder/bowel dysfunction )
What is the prognosis of ADEM?
Maximum disability 4-7 days; severe phase overall lasts 2-4 weeks
Most fully recover
If ADEM recurs after 3 months, what conditions must you consider?
MS
NMO
Recurrent ADEM (but not if >2)
List 3 differences between ADEM and MS
- ADEM <10 years, MS >10 years
- ADEM: Encephalopathy, vomiting fever at presentation
- ADEM: Bilateral ON, MS: unilateral ON
- ADEM: Multifocal, widespread lesions, MS: isolated lesions
- ADEM: CSF-pleocytosis, MS: oligoclonal bands
List 3 clinical features of adrenoleukodsytrophy
Present 5-15 years Academic difficulties Behavioural disturbance -Can be mistaken for ADHD Seizures Visual disturbance Ataxia Poor handwriting
How is adrenoleukodystrophy inherited?
X-linked
Genetics of Duchene’s
X-linked recessive
In-frame deletion = partial dystrophin production (BMD)
Frame-shift mutation - absent protein (DMD)
30% de novo
DMD gene on Xp21
When is the clinical onset of weakness in DMD?
2-3 years of age
What is the pattern of weakness in DMD?
Proximal before distal
Lower before upper
List 2 physical exam features consistent with DMD
Gower’s sign
Waddling gait
Lumbar lordsosis
Calf pseudohypertrophy
When are patients with DMD typically wheel chair bound?
12 years
List 5 complications associated with DMD
Progressive scoliosis Contractures Malignant hyperthermia Fractures due to falling Dilated cardiomyopathy Arrythmias Hypoventilation Frequent pulmonary infections Aspiration risk Intellectual disability
How do you make diagnosis of DMD?
Molecular testing for dystrophin gene mutation
Elevated CK
Muscle biopsy if PCR normal
Treatment of DMD
Multidisciplinary team
Neurology
- Steroid treatment (deflazacort (starting age 5))
- Bone density scan
- Muscle strength testing
Orthopedics
- Monitor for scoliosis, achilles tightening
- Manage fractures from falls
Cardiology
- Monitor for DCM
- Echo Q2 years <10, then yearly >10
- ECG
Physiotherapy
- Passive stretching
- Night splints
- Chest physio
Respirology
- PFTs
- PCO2
- Monitor for nocturnal hypoventilation
List 2 differences between DMD and BMD
BMD-age of onset later (15 years), LD less common, cardiomyopathy more evident
Specific biopsy finding in DMD
Immunohistochemical staining shows abnormal dystrophin molecule
What 2 things do you want to know to help with genetic counseling in DMD?
- Plan to have more kids?
- Family Hx DMD
o Mom with one other affected relative in FHx in obligate carrier
o Mom with no FHx but multiple affected sons has either germline mutation or is mosaic carrier including germline
o Mom with no FHx and only one affected son means proband may have de novo mutation
Anatomic differential of neonatal hypotonia
Central:
CNS
- Metabolic (glycogen metabolism, carnitine def, peroxisomal, mitochondrial…)
- Genetic (T21, Fragile X, PWS, Kabuki syndrome)
- Cerebral dysgenesis
- HIE
Peripheral:
Anterior horn cell disorder
-SMA
NMJ disorder
-Transient neonatal myasthenia, congenital myasthenia, infant botulism, MgSO toxicity,…
Congenital myopathies
-Nemaline myopathy…
Muscular dystrophies
-Congenital muscular dystrophy, CMD with brain abN (walker-warburg, muscle-eye-brain Dz, Fukuyama dz), Congenital myotonic dystrophy
Describe the different type of SMA
SMA type 1
- Presents in neonate (0-6 months)
- Prenatally ↓ fetal movements
- Never sit
SMA 2
- Presents between 3 and 15 months of age
- Never stands
SMA 3
- Presents after 1 year of age
- Can stand and walk
SMA4
-Adult onset
Describe 3 clinical features of SMA syndrome
Diffuse symmetric proximal muscle weakness
LE >UE
Absent reflexes
Arthrogryposis if prenatal onset
Fasiculations of tongue***
Alert expression
Bell shaped chest deformity (intercostals more affected than diaphragm)
How do you diagnose SMA?
Genetic molecular testing for mutation
If normal, confirm with muscle Bx
How is myotonic dystrophy inherited?
AD, usually from mother
What signs should you look for in a mother a child with suspected myotonic dystrophy?
Frontal balding
Mouth opening
Hand myotonia when shake it
Dull cognition
Describe the clinical features of congenital myotonic dystrophy (or congenital DM1)
Profound hypotonia Facial diplegia Characteristic face-tented upper lip, thin cheeks, temporalis wasting High arched palate Doliocephaly Decreased DTRs Arhtyrogroposis Respiratory failure Myotonia not present until >1 year
List 3 clinical features of juvenile myotonic dystrophy (juvenile DM1)?
**Progressive wasting of distal muscles
SCM atrophy
Gowers sign
***DTRs preserved
Dysarthria
Myotonia usually not evident until age 5 yr
List 3 non-muscular complications of juvenile myotonic dystrophy
GI-slow gastric emptying, constipation Cardiac-heart block, arrythmia Endocrine-hypothyroidism, DM, arenal insufficiency, delayed puberty Cataract Low IgG Intellectual impairment
How do you diagnose myotonic dystrophy?
Molecular genetic testing DM1/DM2
Describe the clinical features of congenital muscular dystrophy
Similar to congenital myotonic dystrophy, but less common! Hypotonic Weak (more axial/proximal) ↓ DTRs Facial weakness Difficult feeding Arthrogriposis (contracture 2+ joints at birth) Elevated CK
Name 3 types of congenital myopathy
Nemaline rod
Central core disease
Myotubular myopathy
How do you distinguish between congenital myopathy and congenital myotonic dystrophy
Both have same clinical features BUT in
congenital myopathy-mother is normal and multisystem disorder!
How do you diagnose nemaline rod myopathy?
Muscle biopsy
List 3 risk factors for ONTDs
Folic acid deficiency
AEDs (VPA, carbemazepine), Maternal obesity or diabetes
How much folic acid should mothers with risk factors be taking to prevent ONTDs?
5 mg/day
What is the best prenatal test for ONTDs?
2nd TM U/S (95% sensitivity)
AFP (85% sensitivity)
What is spina bifida occulta?
Cleft in vertebral column without protrusion of SC or meninges
List 3 complications associated with spina bifida occulta
Syringomyelia, Diastematomyelia
Tethered cord
Anorectal and urogenital malformations
List 3 complications associated with meningocele
Syringomyelia, Diastematomyelia
Tethered cord-can lead to spastic diplegia
Hydrocephalus
List 3 reasons why patients with encephalocele are at increased risk of hydrocephalus
Aqueductal stenosis
Chiari
Dandy-Walker
In tethered cord, conus medullaris ends beyond ___?
L2
How do you patients with syringomelia present?
Central cord syndrome
Numbness beginning in shoulders in capelike distribution
Then weakness in UE before LE
What is diastematomyelia?
SC split in half; anatomy of outer half essentially normal, medial half very underdeveloped
Describe the clinical features of diastematomyelia?
Progressive loss of bowel/bladder function
Sensory/motor difficulties in the LEs
Back pain common
List 3 spinal lesions that require imaging for occult spinal dysraphism
Subcutaneous mass or lipoma
Hairy patch
Dermal sinus
Atypical dimples (deep, >5 mm, >25 mm from anal verge)
Vascular lesion, e.g., hemangioma or telangiectasia
Skin appendages or polypoid lesions, e.g., skin tags, tail-like appendages
Scarlike lesions
List 3 conditions associated with myelomeningocele
MSK
- Club feet
- Contractures
- Hip subluxation
GI
- Neurogenic bowel
- Constipation
GU
- Urinary retention
- Constant urinary dribbling
CNS
- Type II Chiari
- > 90% have hydrocephalus
- Hind brain dysfunction-stridor, VCP, apnea, spasticity of upper extremities,
List 3 management priorities in spinal dysraphism
1) Surgery several days after birth
2) Shunt for hydrocephalus
3) CIC
4) Periodic urine cultures and assessment of renal function
5) Bowel regimen
3 things you would tell mother with a previous child with myelomeningocele who is planning to have another child
Higher risk of recurrent NTD due to previously affected pregnancy
Folic acid 4-5mg daily 1 mo prior and for 1st TM after conception
Offer Amniocentesis at 16 weeks for AFP or Screening U/S at 18-20 weeks (MSAFP at 15-16 weeks not as sensitive)
Myelomeningocele in what area is most likely to be associated with lower limb paresis?
Higher up, worse outcomes
What sort of imaging should you do for spinal dysraphism?
Spinal U/S <6 months
MRI spine >6 months
4 Risk factors for developing epilepsy after febrile seizure
Complex febrile seizure
Developmental delay
Family history of epilepsy
Febrile seizure within 1st year of life
List 4 types of treatable neonatal seizures
- Pyridoxine dependent seizures
- Biotinidase deficiency
- Folinic acid responsive seizures
- Glucose transporter type 1 syndrome
- Pyridoxal phosphate dependent seizure
List 4 causes of raised ICP
Tumour
CSVT
Pseudotumour cerebri
Meningitis/encephalitis
Best treatment for tension headaches
Acetaminophen
What is a Arnold Chiari type II malformation?
Herniation of the cerebellar tonsils, caudal brainstem, and the fourth ventricle through the foramen magnum
Associated with myelomeningocele
and hydrocephalus
List 3 conditions associated with Arnold Chiari type II malformation (other than myelomeningocele and hydrocephalus)?
Hypoventilation
Vocal cord paralysis
Bradyarrhytmias
Clues to central vs peripheral causes of neonatal hypotonia
Central:
- Dysmorphisms
- Encephalopathic
- Normal strength
- Hyperactive or normal reflexes
- Fissting, scissoring
- Seizures
Peripheral:
- Alert
- Profound weakness
- Hyporeflexia
- Fasciulations
- Muscle atrophy
Work up for neonatal hypotonia
- Sepsis – urine, blood , CSF culture
- Metabolic – lytes, glucose, LFTs, ammonia, RFTs, gas, plasma amino acids, urine organic acids, lactate, pyruvate, ammonia, acylcarnitine profile, CK
- TORCH titres, urine for CMV if calcifications, HSM
- Karyotype if dysmorphisms
- Array comparative genomic hybridization
- Methylation studies for imprinting defects
- Mutation analysis for known disorders (SMA, mytonic dystrophy)
- EP studies, EMG studies, muscle biopsy
- MRI/MRS
