Neurology Flashcards
What is the criteria for diagnosis of neurofibromatosis type I?
2 or more of the following:
- >= 6 cafe au lait spots
>> Prepubertal: >5mm
>> Postpubertal: >1.5cm
- >= 2 neurofibromas of any type or one plexiform neurofibroma
- >= 2 Lisch nodules of the iris
- Optic glioma
- Freckling of the inguinal or axillary region
- A distinctive bony lesion: sphenoid dysplasia, cortical thinning of the bone
- 1 confirmed case in a first-degree relative
C: Cafe au lait spots (at least 6)
A: Axillary freckling
F: Fibromas
E: Eye (Lisch nodules)
S: Skeletal lesions - sphenoid dysplasia
P: Parents - positive family history
O: Optic glioma
What is the mode of inheritance of neurofibromatosis type I?
Autosomal dominant
- 50% are the result of sporadic/new mutations
What is the mode of inheritance of neurofibromatosis type II?
Autosomal dominant
What is the criteria for diagnosis of neurofibromatosis type II?
Either:
- First degree relatives with NF-2 confirmed
- Any of the following:
>> Neurofibroma
>> Meningioma
>> Glioma
>> Schwannoma
OR
- Bilateral vestibular schwannomas +/- Posterior subcapsular cataracts
What are the clinical features of tuberous sclerosis?
- *Cutaneous lesions**
- Ash leaf spots: better seen under Wood’s light
- Shagreen patches: isolated raised plaque over the lower back and buttocks
- Adenoma sebaceum: often malar distribution
- *Brain/Neurological lesions**
- Cerebral cortical tubers
- Subependymal nodules
- May evolve into giant cell astrocytomas >> obstructive hydrocephalus
- Seizures (infantile spasms very responsive to vigabatrin >> look out for visual field defects in long-term use)
- Mental retardation
- *Others**
- Cardiac rhabdomyomas
- Kidney angiomyolipomas
- Polycystic kidneys
- Subungal fibromata
- Phakomata: dense white areas on retina from local degeneration
What is the mode of inheritance of tuberous sclerosis?
Autosomal dominant
>> 50% are new/sporadic mutations
What is the mode of inheritance of Sturge-Weber syndrome?
Sturge-Weber disease is NOT inherited, but is congenital.
How does Sturge-Weber syndrome present?
Extensive port-wine stain involving the V1 area: usually present at birth
- *Eye abnormalities**
- Neonatal glaucoma
Leptomeningeal/brain abnormalities
- Angiomatous malformations of the brain
>> Contralateral hemiparesis
>> Contralateral hemiatrophy
- Seizures
- Mental retardation
- Microcephaly
- Cortical blindness
What are the possible investigations to help confirm the diagnosis of neurofibromatosis?
- Slit lamp examination for Lisch nodules
- MRI brain, orbits and spinal cord for neurological lesions
(deep plexiform neurofibromas) - Genetic testing
- Excision/biopsy of any lesions suggesting malignant changes
What is the general management plan for neurofibromatosis?
- Genetic counseling
- Mainly SUPPORTIVE
- Annual comprehensive vision exams for signs of optic glioma (usually till 8 years)
- Orthopedic surgery for skeletal abnormalities such as scoliosis, tibial bowing etc.
>> Screening for phaeochromocytoma with urine catecholamine measurement is indicated for any NF1 patient who will undergo general anesthesia (phaeochromocytoma is related to mutations of the genes NF-1, RET, VHL, SDHN and SDHD)
What are the possible causes of headache in children?
Primary
- Migraine with aura
- Migraine without aura
- Tension-type headache
- Cluster headache
Secondary
- Infectious
>> CNS infections
:: Meningitis
:: Encephalitis
:: Brain abscess
>> Non-CNS/ENT infections
:: Orbital abscess
:: Otitis media
:: Sinusitis
:: Pharyngitis
:: Dental infections
- Increased ICP
>> Tumours
>> Hydrocephalus
>> Intracranial hemorrhage
>> Idiopathic intracranial hypertension
- Others
>> Hypertensive encephalopathy
>> TMJ dysfunction
>> Poisoning: carbon monoxide, drugs etc.
What are the four patterns of headaches?
- Acute
- Acute-recurrent
- Chronic non-progressive
- Chronic progressive
What are the physical signs of increased intracranial pressure in children?
- *General examination**
- Irritability/Lethargy
- Poor feeding >> weight loss?
- Vomiting >> dehydration?
- Episodic bradycardia and apnea
- *Head examination**
- Increased head circumference
- Bulging fontanelle
- Widened sutures: “cracked-pot” percussion
- Scalp vein dilation
- *Eye examination**
- Sunset eye sign
- Papilloedema
What are the red flag signs of headaches?
- New headache
- Worst headache of their lives
- Acute onset
- Recurrent and localized
- Worse in the morning
- Worse with bending over, coughing and straining
- Associated with nausea and vomiting
- Focal neurological symptoms
- Disturbed sleep
- Change in level of consciousness
- Sudden mood changes
- Constitutional symptoms
- Withdrawal from social activities
What investigations can be helpful in determining the cause of headache in children?
- *Blood tests**
- CBC with differential count: signs of infection
- CRP: infection
- ESR: inflammation
- TFT: to R/O Hashimoto’s encephalopathy
Other laboratory tests
- Lumbar puncture to rule out:
>> CNS infection
>> Subarachnoid hemorrhage
>> Pseudotumor cerebri/idiopathic intracranial HTN
- Always do imaging to R/O SOL before LP if possible
Neuroimaging
- CT for fast dx of intracranial hemorrhage and SOL
- MRI for details
- To look out for
>> Intracranial hemorrhage
>> Space-occupying lesions
>> Hydrocephalus
>> Congenital malformations
>> MRI evidence of CNS infections
What is meningism?
- *Triad of:
- Nuchal rigidity
- Headache
- Photophobia**
Indicates:
- Meningitis
- Subarachnoid hemorrhage
- Other meningial diseases
Signs include
>> Kernig’s sign
>> Brudzinski’s sign
What are the presenting features of migraine?
- *Character of headache**
- Usually bilateral headache at the temporal/frontal area
- Pulsatile headache
- Duration 1-72 hours
- Relief with rest in a quiet and dark place
- *Associated symptoms**
- *- Photophobia
- Phonophobia**
- GI disturbances: nausea, vomiting, and abdominal pain
- *Aura
- Negative phenomena: hemianopia, scotoma
- Positive phenomena: fortification spectra**
What are the presenting features of cluster headache?
- *Character of headache**
- Episodic headaches: several each day for 4-8 weeks
- Followed by relief for 6-12 months
- Deep, continuous and severe headache
- *Associated symptoms**
- *- Ipsilateral lacrimation
- Rhinorrhea**
- Miosis/ptosis
- Conjunctival infection
- Horner Syndrome
What is the management plan for migraine?
Conservative treatment
- Patient education
- Avoidance of triggers
>> Poor sleep
>> Stress
>> Caffeine
>> Chocolate
- Rule out menstrual migraine
- Encourage exercise
- Magnesium supplementation
Abortive treatment
- Analgesics: ibuprofen
- Triptans
>> Nasal sumatriptan
>> Nasal zolmitriptan
- Antiemetics if necessary
Prophylactic treatment
- Beta-blockers (e.g. propranolol)
- Cyproheptadine
- Anti-histamines
- Anti-depressants
>> Amitriptyline
>> Trazodone
- Anticonvulsants
>> Topiramate
>> Valproate
- Calcium channel blockers
What is the management for cluster headaches?
- *Abortive treatment**
- *- Oxygen
- Triptans**
- Ergot alkaloids
- *Prophylactic treatment**
- Calcium channel blockers
- Anti-depressants
- Anti-convulsants
- *Surgical treatment**
- Nerve blocks
- Ablative procedures
- Brain stimulation
What are the presenting features of tension-type headache?
- Bilateral pressing tightness: aching, non-pulsatile
- Lasts 30min - days
- *- No nausea or vomiting**
- *- Not aggravated by physical activity**
What are the symptoms of increased ICP?
- Diffuse early morning headaches
-
Headache worsened by:
>> Coughing
>> Sneezing
>> Valsalva maneuvre - Chronic progressive headache
- Early morning vomiting
- Irritability/lethargy
What is the age of peak incidence for meningitis in children?
6-12 months
90% of meningitis occur in children <5 years of age
What are the main causative organisms of meningitis in children?
AGE-DEPENDENT
Bacterial causes
- Neonates
>> E. coli, Klebsiella
>> GBS
>> Listeria
>> Others: staphylococcus aureus, H. influenza
- 1m - 6y
>> Neisseria meningitidis
>> Streptococcus pneumoniae
>> Hemophilus influenzae type B (Hib)
- Children >6y of age
>> Neisseria meningitidis
>> Streptococcus pneumoniae
- Adults
>> Streptococcus pneumoniae
>> Neisseria meningitidis
>> Gram-negative bacilli
Viral causes
- ENTEROVIRUSES (including polio)
- Herpes viruses:
>> HSV
>> CMV
>> VZV
Fungal causes
Parasitic causes
What is the management of suspected meningitis in a child?
Supportive treatment
- Investigations
>> Blood
:: CBC with differential
:: CRP/ESR
:: RFT: for any SIADH/electrolytes/baseline
:: LFT: baseline
:: Blood culture
** >> Lumbar puncture
:: For definitive diagnosis**
:: Stain and culture
:: WBC count and differential
:: RBC count
:: Glucose
:: Protein
:: Acid-fast stain if TB suspected
:: Latex agglutination/PCR if viral suspected
>> Neuroimaging before LP
>> Urine in neonates
:: Urinalysis
:: Culture and stain - Empirical antibiotics
>> After taking specimens for culture
>> To cover penicillin-resistant pneumococcus and Neisseria meningitidis
>> **Typical regimen: IV penicillin/3rd gen ceph (cefotaxime) + IV vancomycin - +/- Dexamethasone to help decrease neurological sequelae**
- Acyclovir for HSV meningitis (when proven)
Maintain high alert for hydration status and electrolyte disturbances as CNS infections may precipitate SIADH – fluid restriction if any related concerns
What are the normal CSF profiles for children and infants respectively?
- *Newborn**
- WBC: 0-30
- Neutrophil %: 2-3
- RBC: 0-2
- Glucose: 30-120 mg/dL
- Protein: 20-150 mg/dL
- *Children**
- WBC: 0-6
- Neutrophil %: 0
- RBC: 0-2
- Glucose: 40-80 mg/dL
- Protein: 20-30 mg/dL
What is the typical CSF profile of bacterial meningitis?
Turbid CSF
Elevated opening pressure (>20cmH2O)
WBC: >1000
Neutrophil %: 2-3
RBC: 0-10
Glucose: 100 mg/dL (increased)
>> Characterized by neutrophil-dominant extremely high WBC counts with decreased glucose and increased protein concentrations
What is the typical CSF profile for viral meningitis?
Clear CSF
Normal opening pressure
WBC: 100-500
Neutrophil %: 30 mg/dL (normal or increased slightly)
Protein: 50-100 (normal or increased slightly)
>> Characterized by mildly elevated lymphocyte-dominant WBC counts with normal glucose and protein concentrations
What is the typical CSF profile for HSV meningitis?
Clear CSF
Normal opening pressure
WBC: 100-1000
Neutrophil %: 30 mg/dL
Protein: >75 mg/dL
>> HSV is characterized by increased WBC count in CSF
What is the typical CSF profile for TB meningitis?
Turbid/clear CSF
WBC: slightly elevated/variable
Neutrophil %: Lymphocyte-dominant
RBC: normal
Glucose: elevated +++++
Protein: elevated +++++
>> Characterized by mildly elevated lymphocyte-dominant WBC counts with extremely elevated glucose and protein concentrations
What are the complications of meningitis?
Short-term
- SIADH
- Brian abscess
- Subdural empyema/effusion
- Disseminated infection
>> Osteomyelitis
>> Septic arthritis
>> Abscesses
- Shock/DIC (disseminated intravascular coagulopathy)
>> Meningococcemia!
- *Long-term**
- Hearing loss
- Neuromotor/cognitive delay
- Learning disabilities
- Neurological deficits
- Seizures
- Hydrocephalus
What are some differential diagnoses for infectious encephalitis?
- ADEM (acute disseminated encephalomyelitis)
- Trauma/intracranial hemorrhage
- Malignancy
-
Autoimmune encephalitis
>> NMDAR antibodies
>> VGKC antibodies -
Metabolic encephalopathy
>> Hypoglycemia
>> Uremia
>> Hashimoto’s encephalopathy
>> Inborn errors of metabolism - Toxic encephalopathy
>> Lead poisoning
>> Reye syndrome from aspirin
>> Other drugs - Idiopathic intracranial hypertension (pseudotumor cerebri)
What are the possible causes of hydrocephalus in childhood?
- *Congenital**
- Congenital cerebral aqueduct stenosis
- Secondary gliosis from congenital infection
- Dandy-Walker malformation
- Arnold-Chiari malformation
- Myelomeningocele
- Craniosynotosis
Acquired
- CNS infections: Meningitis
- Intracranial hemorrhage
>> Subarachnoid hemorrhage
>> Intraventricular hemorrhage
- Intracranial masses
>> Arteriovenous malformations
>> Neoplasms/SOL
- Craniosyntosis
What is the most common cause of seizures in children?
Febrile seizures
What is the typical age for febrile seizures?
6 months - 6 years
What are the criteria for atypical/complex febrile seizures?
Any one of the following:
- Duration >15 minutes
- Focal features/focal onset
- Prolonged post-ictal phase
- Neurological deficit after seizure
- Recurrent seizures: >1 episode in 24-hour period
- Previous neurological impairments
What is a typical febrile seizure?
- Short (almost always >15mins)
- Either a GTC or a generalized clonic seizure
- No signs of CNS infections or inflammation
- No history of non-febrile seizures
What do we look for in the history for a child with febrile seizures?
- Focus of fever
- Description of seizure: focal VS. generalized
- History of LOC
- History of trauma
- Medications
- Family history
- Development
What is the management for febrile seizures?
REASSURE THE PATIENTS AND PARENTS
- Febrile seizures do NOT cause brain damage
- Very small risk of developing epilepsy
>> 9% in child with multiple risk factors
:: Neurological abnormalities before seizure
:: Multiple simple febrile seizures
:: Family history of complex febrile seizures
>> 2% in simple febrile seizures
>> 1% in general population
- 33% of recurrence
>> Mostly within the first year
>> Mostly in children <1 year of age
Treat the underlying cause of fever
Antipyretics for symptoms only: do NOT prevent seizures!
What are the possible causes of seizures in children?
- Febrile seizures
- Idiopathic/Epileptic syndromes
- Intracranial causes
>> Congenital causes
:: Neurocutaneous syndromes (TS)
:: Anatomic abnormalities
~ Cortical dysplasia
~ Schizencephaly
~ Polymicrogyria
>> Infections
:: Meningitis
:: Encephalitis
:: Cerebral abscess
>> Trauma
>> Vascular
:: Stroke
:: Hemorrhage
:: Arteriovenous malformation
>> Hypoxic-ischemic encephalopathy
>> Tumours
- Extracranial causes
>> Metabolic
:: Hypoglycemia
:: Hyponatremia
:: Hypocalcemia
:: Storage diseases
>> Systemic hypoxia
>> Toxins and toxin withdrawal
What is West syndrome?
Onset at 4-8 months of age
- *Triad of the following:
- Infantile spasms (flexion VS. extension salaam spasms)
- Psychomotor developmental arrest
- Hypsarrhythmia**
What is Lennox-Gastaut syndrome?
Onset at 1-7 years (3-5 years) of age
- *Triad of the following:
- Multiple seizure types
- Diffuse cognitive dysfunction
- EEG: Slow generalized spike and slow waves**
What are the possible treatments for West syndrome/infantile spasms?
- Vigabatrin (particularly useful for tuberous sclerosis; be aware of visual field defects)
- ACTH/corticotropin
- Corticosteroids
- Benzodiazepines
What are the possible treatments for Lennox-Gastaut syndrome?
Ketogenic diet
- *Anti-epileptic drugs**
- Valproate
- Lamotrigine
- Topiramate
- Clobazam
- Benzodiazepines
- >> Avoid carbamazepines as they may precipitate drop attacks CNX stimulation*
- *Epileptic surgery**
- Corpus callosotomy
- Lesional epilepsy surgery
What are the side effects of phenytoin?
- *Systemic and Dermatological**
- Stevens-Johnsons syndrome
- Toxic epidermal necrolysis
- Gum/gingival hypertrophy
- SLE-like symptoms
- Hypotension
- Teratogenic
- *Neurological**
- Peripheral neuropathy
- Headache
- Nystagmus
- Sedation
- *Gastroenterological**
- Nausea and vomiting
- Constipation
What are the side effects of valproate?
- *Systemic**
- Alopecia
- Thrombocytopenia
- Tremor
- Hypothermia
- *Neurological**
- Headache
- Somnolence
- Diplopia
- Encephalopathy
- *Gastroenterological**
- Nausea and vomiting
- Diarrhea
- Hepatic failure
- Pancreatitis
How is the prognosis for West syndrome?
Poor
- 50-90% develop other seizures
- 27-50% progress to Lennox-Gastaus syndrome
- Developmental retardation in 85%
How is the prognosis for Lennox-Gastaut syndrome?
Poor
- Poor response to therapy
- Neurodevelopmental arrest/regression
- Behavioural disorders
What are the presenting features of juvenile myoclonic epilepsy?
Age of onset: adolescence-adulthood (12-16 years)
Types of seizures
- Myoclonic seizures within first hour of waking (flinging cereal around at breakfast)
- Daytime generalized tonic-clonic seizures
- Absence seizures
What is the typical EEG pattern for absence seizures/childhood absence epilepsy?
Generalized 3/second spike and wave discharge (VT)
