Neuro Flashcards
Differentials for seizure and for LOC?
Seizures: febrile convulsion, non-epileptic attack disorder (pseudoseizures), epilepsy, meningoencephalitis, infection (sepsis, abscesses, subdural empyemas), tumour, toxins, metabolic (e.g. hypoglycaemia, urea cycle defects), head injury.
LOC: breath-holding attacks or spasms, reflex anoxic seizures, vasovagal syncope, cardiac arrhythmias.
What is a febrile convulsion? Who does it affect?
6 months – 6 yrs (6 months – 3 yrs most common). ~1 in 20.
Most common presentation of seizures in ED (~5% of pre-school children).
Associated with ≥38°C, in absence of CNS infection, metabolic imbalance or neurological condition.
Aetiology not fully understood, but genetics (familial predisposition) and infection are important factors. Believed to be due to viral illness however bacterial infection should always be considered.
Often occur with tonsillitis, otitis media, herpes simplex, shigella, rotavirus gastroenteritis or roseola.
How are febrile seizures classified?
- Simple: generalised tonic-clonic seizure ≤15 mins, not recurring within 24 hours
- Complex / atypical: >15 mins, focal, or recurring within the same febrile illness
- Status: >30 mins
How are febrile convulsions diagnosed?
Management?
Clinical ∴ no specific Ix needed: initial Ix to rule out hypoglycaemia or UTI in infants should be taken as general precautions.
Simple febrile seizures: rapid + full neurological recovery. Always consider meningoencephalitis in child with fever + seizures (potentially life-threatening).
?1st presentation of epilepsy if no clear neurological focus.
Most children presenting with febrile convulsions are well by the time they attend ED + have a clear focus. In these cases, management:
- Antipyretics: paracetamol & ibuprofen ↓ discomfort, not prevent further convulsions
- Education & reassurance: parents should understand risks of recurrence & how to manage future febrile seizures (recognition and reduction of fever by undressing & giving anti-pyretic), know how to keep child safe during seizure, to seek medical advice if it lasts <5 mins, and to call an ambulance if it lasts longer
When to consider admission for febrile convulsions?
Consider admission if: • First febrile seizure • Seizure >15 mins • Focal seizure • Recurring with same febrile illness within 24 hours • Incomplete recovery after 1 hour • <18 months old • Parental anxiety • Suspected serious cause for infection (e.g. pneumonia) • No apparent focus of infection
If none of the features below: green (self-care advised)
If a febrile seizure lasts >5 mins?
Benzodiazepines (e.g. buccal midazolam, PR diazepam) can be effective
Prophylactic anti-epileptics are not routinely recommended, even if seizures are recurrent.
Prognosis of febrile convulsions?
Overall recurrence risk ~1 in 6.
associated with good neurological outcome and there is a 2% risk developing epilepsy (compared to 1% risk in those without Hx of febrile seizures).
Complex febrile seizures have a higher risk of epilepsy.
Epilepsy - aetiology?
0.05% incidence, 0.5% prevalence.
Recurrent (at least 2 unprovoked episodes, 24 hours apart) seizures thought to be of electrical origin in the brain. The term describes a predisposition to have epileptic seizures. Also possible for children who do not have epilepsy to have such seizures. Six main causes:
- Idiopathic: 70%
- Genetic: e.g. channelopathies
- Structural: e.g. tuberous sclerosis, cortical malformation, medial temporal lobe epilepsy with hippocampal sclerosis
- Metabolic: e.g. pyridoxine deficiency
- Immune: autoimmune-mediated CNS inflammation e.g. NMDAR antibody encephalitis or VG-K+ channel antibody encephalitis
- Infectious: often has a structural correlate e.g. HIV, TB, cerebral malaria or cerebral toxoplasmosis
Types of epilepsy in children?
Generalised epileptic seizures (both hemispheres + accompanied by LOC)
- Tonic clonic: most common: sudden rigidity, stiffening + muscle contraction followed by rhythmic twitching or muscle jerking: usually last for 1 minute, and EEG shows generalised symmetrical waveform
• Tonic: generalised increased tone
• Atonic: jerk follows sudden loss of tone
• Clonic: rhythmical muscle contraction + subsequent relaxation
• Absence: sudden loss of motor activity which spontaneously recovers – flickering of eyelids, staring, and transient LOC may occur
• Myoclonic: one or several brief arrhythmic muscle jerks, often localised to one body part: neck, trunk or limb, repetitive and spontaneously recovers. Sometimes visible movement of affected region not seen but child can feel shock-like sensation in muscles
Partial epileptic seizures (one hemisphere, do not always cause LOC)
• Focal / simple partial: can be motor, sensory or autonomic (sweating, nausea), or psychic (déjà vu altered mood)
• Complex partial (temporal lobe epilepsy): starts in one region but also affects other regions controlling consciousness – characterised by reduced consciousness and often preceded by aura including automatisms e.g. lip smacking
• Temporal: auditory or sensory disturbances, déjà vu (feeling of familiarity) and jamais vu (feeling of unfamiliarity)
• Occipital: visual disturbance associated with oculomotor signs
• Focal seizure with secondary generalisation
Also: Epilepsy Syndromes: epilepsies presenting with ‘electro-clinical’ pattern of clinical features + characteristic EEGs
Outline West syndrome
Infantile spasms: uncommon but serious form of epilepsy, typically 3-8 months old: ‘salaam attacks’: sudden flexor spasms, bending at waist + nodding head > subsequent arm extension.
Movements last 1-2 secs, often occur in clusters. EEG diagnostic: hypsarrhythmia - chaotic, irregular high amplitude waves + spikes, with background of disorganised + chaotic electrical activity.
Developmental delay or even regression often associated. Also associated with tuberous sclerosis.
Tx options: corticosteroids, ACTH + vigabatrin.
Outline absence epilepsy
Childhood absence epilepsy usually present 4-9 years, girls > boys.
Typical seizure lasts 5-20s, usually involves arrest of movement + awareness, staring into space blankly without loss of tone. Can occur multiple times a day + sometimes associated with purposeless movements of mouth + eyes (eyelid flickering, lip smacking), called automatisms.
Development usually normal but learning may be impaired due to the episodes. Ictal EEG typically shows generalised + bilaterally synchronous 3-per-second spike + wave discharges.
Spontaneous remission often occurs in adolescence.
Ix for epilepsy?
Clinical diagnosis (detailed history, eyewitnesses), but may be supported by:
• Home video recordings
• EEG (support diagnosis + define syndrome)
- sleep deprived EEG or telemetry may be indicated to increase sensitivity (if high clinical suspicion of focal or generalised epilepsies).
- Intracranial EEG gold standard for identifying neuronal activity (+ if surgery being considered, can be used to localise exact epileptogenic zone)
• Imaging
- MRI recommended if epilepsy <2 years + for focal epilepsy, myoclonic epilepsy, intractable seizures, loss of previous good control, continuing seizures despite 1st line medication, associated neurological deficits / evolving neurological signs, developmental regression or infantile spasms
- CT: to identify focal structural defect if focal neurological signs are identified
- fMRI, PET & SPECT not used except in specialist cases – identifies areas of hyperactivity and metabolism in the brain – used to assess brain involvement and plan neurosurgical resections
• Genetic studies: to identify known epilepsy syndromes e.g. gene deletions related to ion channels
Management of epilepsy?
- Education: diagnosis, action plan + emergency plan with relatives + school: recognising + managing seizures, supervision (bathing, swimming, outdoor activities) – driving and future careers important in adolescents
- MDT: always needed for complex epilepsy regardless of developmental needs e.g. epilepsy specialist nurse, consultant neurologist, local paediatrician, educational psychologist, physiotherapist, OT. Successful therapeutic relationships important – adherence often an issue especially in adolescent patients
- AEDs: likely to initiate by specialist after 2nd seizure: depends on type of epilepsy, tolerability of side effects and treatment goal (eliminating vs reducing seizures) > Sodium inhibition, calcium inhibition, GABA effects
Surgical intervention: potential to benefit selected patients e.g. clearly identified focus of activity, mass triggering the seizure, or recurrent seizures causing significant morbidity despite maximal medication therapy o Resection (remove epileptogenic focus) o Multiple subpial transection (cutting nerves in outer layers of brain, preserving vital function concentrated in deeper layers of brain) o Corpus callosotomy: surgery to corpus callosum - contain any seizure in ½ brain
Ketogenic diet: high fat & low carb – intractable epilepsy although mechanism unclear – careful supervision of consultant paediatric neurologist + dietician – can be difficult for children to be adherent
Vagus nerve stimulation: generator implanted under skin below clavicle – connected to thin wire which stimulates vagus nerve at regular intervals to prevent seizures
Deep brain stimulation: fitting a device with neurostimulator that stimulates part of the brain where seizures originate
Outline which AEDs are used for which seizures?
Focal:
- 1st: Carbamazepine or lamotrigine
- Adjunctive: levetiracetam, oxcarbazepine or sodium valproate
Absence
- 1st: ethosuximide or sodium valproate
- 2nd: lamotrigine
Tonic or atonic
- 1st: sodium valproate
- 2nd: lamotrigine
Generalised tonic-clonic
- 1st: sodium valproate
- 2nd: lamotrigine
Myoclonic
- 1st: sodium valproate
- 2nd: levetiracetam or topiramate
Infantile spasms: refer to tertiary paediatric specialist, 1st: corticosteroid or vigabatrin
Complications of epilepsy?
Acute: prolonged, uncontrolled seizure – emergency as can lead to cardiac or respiratory arrest – as seizure becomes more prolonged, increased risk of cerebral damage – seizures also put a child at risk of physical injury from trauma e.g. haematomas, bruising, abrasions, burns
Long-term: small increased risk in mortality, usually related to impaired consciousness – sudden unexpected death in epilepsy (SUDEP) is a risk, particularly in context of uncontrolled seizures or poor compliance – exact mechanism unclear but may relate to cardiac arrhythmias, respiratory arrests or neurogenic pulmonary oedema: anti-epileptic medications come with significant side effects and school absences may be frequent
Prognosis: can depend on type, underlying conditions and structural abnormalities – most children well-controlled seizures and mainstream school, some more complex needs – may require involvement from epilepsy nurse specialist, educational support and support from extended MDT – some childhood epilepsies abate by adulthood.
What is status epilepticus?
Seizure or repeated seizures which last >30 minutes without regaining consciousness. Risk of serious brain injury and respiratory arrest are very high. Senior assistance should be sought immediately and treatment should be escalated.
Management of status epilepticus?
- High flow oxygen, check glucose, ensure patent airway
- IV lorazepam (can give 2nd dose after 10 mins), if no IV access: buccal midazolam
- If persists IV phenytoin (or phenobarbitone if already on), paraldehyde can be given if available while preparing phenytoin
- Rapid sequence induction with thiopentone and intubation
What are breath-holding attacks?
Usually <3 years, (can be age 1-6), provoked by temper or frustration, on getting upset, may hold breathe, go cyanotic and then go limp > loss and regaining of consciousness.
Eyes are closed during episodes (if tonic-clonic seizure, eyes are open). Episodes resolve spontaneously and no intervention is required.
- Cyanotic = most common type (goes blue) – caused by change in breathing usually in response to feeling angry
- Pallid = goes pale, caused by slowing of heart rate often in response to pain
What are reflex anoxic seizures?
vasovagal syncope?
cardiac arrhythmias?
Any age but peak incidence 6 months – 2 years, usually triggered by event e.g. pain, minor head trauma, cold or fever), causing child to have vagal-induced brief cardiac asystole or bradycardia > syncopal episode where turn pale and fall to floor. Subsequent hypoxia may lead to a seizure, which resolves spontaneously.
Children often have a first degree relative with history of fainting.
Vasovagal Syncope
Inadequate cardiac output to brain may lead to brief LOC – often occurs in warm environments or after standing for long periods – seizure can also occur as part of the syncope
Cardiac arrhythmias: may cause collapse or cardiac syncope – prolonged QT may be present on resting ECG, predisposing to ventricular arrhythmia
Infective causes of meningitis?
Spontaneous or with risk factors: immunosuppression (cancer, chemo, HIV, congenital T-cell deficiency, splenic disease), intracranial foreign bodies (cochlear implants, CSF shunts), trauma (may lead to basal skull fracture)
Viral (2/3rds of all cases) - most enteroviruses (self-limiting).
• Others: EBV, adenovirus, varicella zoster virus (VZV), cytomegalovirus (CMV), measles + mumps.
• Herpes simplex: rare but devastating cause of meningoencephalitis, neonates usually acquire during delivery > maternal secretions). Hallmarks: seizures + liver dysfunction.
Bacterial: dramatic changes: Hib, Men C + PCV vaccines
- <3 months: GBS, Escherichia coli, Listeria
- 3 months – 16 years: streptococcus pneumoniae, Neisseria meningitis (meningococcus), Hib
GBS most common cause of bacterial meningitis, septicaemia + infectious death in <3 months. Usually vertically transmitted + can occur up to 6 months. If mother colonised, low threshold to Tx baby prophylactically/
Strep. pneumoniae: any age but usually <5, higher mortality + neurological sequelae
Meningococcus: usually nasopharyngeal mucosa > bloodstream > CNS. If also septicaemia, associated with non-blanching rash (can consist of petechiae and/or purpura).
TB meningitis: rare in countries with low TB incidence + good BCG uptake, higher risk in some UK inner city areas. Can be difficult to diagnose as children often present with vague non-specific symptoms (generally unwell, aches/pains, low grade fever for up to 8 weeks. Usually poorer prognosis because of the late diagnosis).
Fungal: rare, more common in immunocompromised. Cryptococcus most common cause.
Symptoms of meningitis?
All ages: seizures, lethargy, irritability, ↓feeding / off food, ↓ urine output, vomiting / diarrhoea, respiratory distress, Fever not always present, especially in neonates..
Children < 1: high-pitched cry, tense fontanelle, ↓ tone, apnoeas, bradycardias, temperature instability
Older children: headache, neck stiffness, photophobia, confusion, muscle pains, positive Kernig’s sign (knee and hip at 90°, extension of knee is painful), Brudzinski sign (less common – neck flexion causes hip flexion)
Non-infective causes of meningitis?
Rare but often missed and can result in significant morbidity. Symptoms tend to be milder, develop more slowly and fail to respond to antimicrobials.
- Malignancies e.g. leukaemia, lymphoma, CNS tumours
- Chemotherapy
- Autoimmune diseases e.g. Kawasaki’s, SLE, vasculitis + connective tissue disease
Blood tests in meningitis?
FBC (elevated WCC and altered platelets in infection)
U+Es: renal function may be compromised from shock with associated electrolyte disturbances. Low sodium may be secondary to SiADH
LFTs: may have hypoxic injury from shock or be directly infected as classically seen in HSV infection
CRP: elevated indicates infection, may not immediately rise, can also be low as a result of liver dysfunction.
Blood culture • Viral PCR • Meningococcal PCR • Enterovirus can be isolated from stool • Lactate: if >2, can indicate compromised end organ perfusion (note: sepsis and meningitis can occur both separately and concurrently)
- Glucose: sepsis may be associated with hypoglycaemia or hyperglycaemia – aids interpretation of CSF glucose
- Blood gas: low arterial pH with low bicarbonate may show a metabolic acidosis
Ix in meningitis (apart from bloods)?
- CT: always if focal neurological signs or evidence of raised ICP (+ normal CT does not exclude raised ICP). Perform in child with closed fontanelles before LP, but not necessary to exclude raised ICP in neonates as raised ICP is generally prevented by open fontanelles
- Cranial USS: considered in neonates as it may identify any intracranial bleeds – as the fontanelles are open, USS can access the brain
LP: indicated in suspected meningitis to confirm diagnosis, determine Abx sensitivities to any bacteria cultured + length of Tx according to organism.
- Absolute contraindications to LP: signs of raised ICP (relative HTN + bradycardia, focal neurological signs, papilloedema, doll’s eyes or fluctuating level of consciousness). Cardiopulmonary compromise, infection overlying the skin, coagulopathy or thrombocytopaenia.
- WCC, protein level, glucose level + opening pressure give an indication of the aetiology. CSF samples can be sent for bacterial culture, meningococcal and viral PCR. Paired glucose from serum and CSF are necessary to help accurately interpret results.
Additional tests: throat swabs, urine culture (UTI can present very non-specifically, particularly in neonates), sputum culture (if possible respiratory focus), stool culture (if possible GI focus), CXR (if any signs of respiratory distress), ECG (not as frequent in children – may be helpful is suspected arrhythmia e.g. irregular rhythm or persistent tachycardia not responding to fluid resuscitation), EEG if associated seizures
Management of meningitis?
ABCDE (if signs of shock, seizures or raised ICP – anaesthetist + senior clinician should be present), children with meningococcal sepsis are likely to require multiple fluid boluses
IV Abx: immediately (as soon as access gained)
o One regimen would be 3rd generation cephalosporin (e.g. cefotaxime), with amoxicillin added if patient is <3 months, to cover listeria
o Macrolide may be considered to broaden cover (e.g. suspected mycoplasma infection)
o Duration guided by response, cultures and microbiology advice- typically 7-10 days.
Antivirals: should be added if HSV encephalitis suspected – should be considered in:
o Recent contact with HSV
o Altered behaviour, cognition or consciousness
o Seizures
o Deranged LFTs
o Severely unwell
Corticosteroids: not indicated if <3 months, in older children some evidence suggests they may reduce pneumococcal meningitis related hearing loss, but evidence of benefit in meningitis generally unclear – routine administration remains controversial (when given, usually a one-off dose prior to antibiotics)
Report to public health authorities: household contacts of the index case should be given prophylactic antibiotics
Acute complications of meningitis?
Septic shock: co-existing septicaemia, presents as tachycardia, respiratory distress, reduced GCS score, pale/cold peripheries & poor urine output
Disseminated intravascular coagulation (DIC): due to sepsis, leading to coagulopathy and widespread bleeding
Raised ICP: results from cerebral oedema and is a very poor prognostic sign – classic symptoms are hypertension, bradycardia, reduced GCS and irregular respiration (Cushing’s triad).
SiADH: elevated concentration of serum antidiuretic hormone (ADH) is a host response to infection, permanent post-infectious scarring may result in long-term hydrocephalus, necessitating a ventriculoperitoneal (VP) shunt
Cerebral abscess / encephalitis / subdural empyema: caused by infection spreading to the brain
Long term complications of meningitis?
- Hearing loss: most common complication of bacterial meningitis, caused by cochlear infection (5-30% of children with meningitis) – hearing assessment within 6 weeks after discharge– if impaired, earlier cochlear implant insertion = better prognosis
- Subdural effusion: more common in infants: 10-30% of children with meningitis – most are asymptomatic, but may result in a bulging fontanelle, enlarging head size and/or seizures
- Neurological complications: learning difficulties, motor and neurodevelopmental deficits
- Renal complications: acute and chronic renal impairment, secondary to septic shock (if there is associated sepsis)
- Orthopaedic complications (rare): amputation, growth plate damage & arthritis due to nerve damage, secondary to septic shock
- Skin complications (rare): may occur secondary to septic shock – reconstructive surgery may be indicated
CSF in meningitis?
Bacterial: Cloudy, low glucose (<1/2 plasma), high protein (>1g/l), WCC = 10 - 5,000 polymorphs/mm³
Viral: Clear, glucose 60-80% of plasma, protein normal or raised, WCC 15 - 1,000 lymphocytes/mm³
TB: slightly cloudy, fibrin web, low glucose (<1/2 plasma), high protein (>1g/l), WCC 10 - 1,000 lymphocytes/mm³
Prognosis of meningitis?
Most children recover fully from viral meningitis
Bacterial has 5-10% mortality and 10% of survivors suffer long-term complications
HSV meningoencephalitis associated with significant morbidity and mortality (70% progress to coma + death if left untreated)
GBS meningitis has poor prognosis, with up to 50% mortality and high morbidity.
What is encephalitis?
Inflammation of brain parenchyma, often occurs simultaneously with meningitis due to close proximity. Consider encephalitis if altered consciousness or behaviour, confusion, or seizures. Most common infectious causes:
• Herpes simplex virus 1 and 2
• Enteroviruses
• Varicella
Herpes simplex encephalitis may be diagnosed based on serum + CSF viral PCR. Characteristic MRI & EEG findings – carries significant morbidity and mortality and if suspected acyclovir should be given.
Chronic encephalitis may occur with HIV or following measles (subacute sclerosing panencephalitis or SSPE). SSPE can have latent period of 6-8 years: progressive condition.
Other causes of encephalitis:
Acute disseminated encephalomyelitis (ADEM): autoimmune mediated inflammatory demyelinating neurological condition, symptoms similar to MS presents at 5-8 years old, acute onset encephalopathy with polyfocal neurological deficits often with a preceding infectious illness or history of immunisation. Relatively uncommon: 3-6 cases each year in UK regional centres.
NMDAR antibody encephalitis (can be associated with malignancy particularly in females)
Voltage-gated potassium channel-complex antibody-associated limbic encephalitis
Rasmussen encephalitis: associated with autoimmune antibodies e.g. anti-GluR3 antibodies
Primary vs secondary headache?
Primary headaches: migraine, tension type headache, less frequently cluster headaches
Secondary headaches: intracranial mass, intracranial bleed e.g. subarachnoid haemorrhage, subdural haematoma, infection e.g. meningitis, sinusitis, encephalitis, ischaemic stroke, benign intracranial hypertension
Majority are primary and self-limiting – since secondary headaches can have significant causes, there should be a low threshold for imaging, particularly in children <5 years.
Indications for CT / MRI in headache?
- Focal neurological features
- Signs of raised ICP
- Headaches which are worse on lying down
- Confusion or altered consciousness
- Change in personality
- Abnormal gait
- Growth failure
- Diplopia or visual field defect
- Facial nerve palsy
- Seizures
- Atypical auras
- Thunderclap headaches
- Known existing secondary cause e.g. intracranial mass
What is migraine? Risk factors?
Most common cause of recurrent headache. May be associated with aura, nausea, vomiting, photophobia & phonophobia. Mechanism remains incompletely understood, but likely to be neurovascular in origin. Risk factors include:
• Family history: 90% children have 1st or 2nd degree relative with recurrent headaches
• Triggers: stress, menstruation, not eating food at regular intervals, irregular or inadequate sleep, dehydration, exercise and weather changes
How to differentiate migraine?
Recurrence - episodic character of the headache can help distinguish from tension type headaches and secondary headaches.
• Migraine with aura: consider more rarely TIA or stroke:
o Onset (migraine aura is more gradual in onset, as opposed to the sudden onset of visual disturbance in TIA & stroke)
o Duration (TIA & migraine are fully reversible) o Imagin
Migraines are rare in young children – low index of suspicion for brain tumour
If headache lasts >72 hours: termed status migrainosus.
ICHD-III (International Classification Headache Disorders)
Migraine without aura (common migraine):
• Most common (~90% of cases)
• Characterised by focal, throbbing headache
Migraine with aura (classical migraine):
• 10% of cases
• Photopsia (bright flashes of light): most common type of aura in children– going to a dark room can be helpful + sleeping can relieve the episode
• Rare auras include dysphasic auras (inability to speak) and hemiplegic aura (transient unilateral weakness), which can last for several hours to days
Conservative Management
Avoid triggers and select strategies for dealing with attack (e.g. lying still in a dark room)
Medical Management
• Acute episodes:
o Combination therapy: triptans (e.g. sumatriptan) and NSAIDs / paracetamol
o Antiemetics can be given to relieve nausea and vomiting
• Prophylaxis:
o Beta blockers (e.g. propranolol)
o Topiramate (targets voltage gated ion channels and neurotransmitter activity)
o Pizotifen (serotonin antagonist)
Prognosis: generally improve with age, however, around 50% will continue into adulthood. Small increased risk of ischaemic stroke & very small increased risk of mental health problems e.g. depression.
Tension Type Headache
Usually associated with stress: at least 10 headaches with durations of 30 mins 7 hours required for formal diagnosis – both muscular and psychogenic factors are implicated in causing the pain. Classically described as: symmetrical, gradual onset, non-throbbing, feel like a band or pressure / tightness, unaffected by physical activity.
Management with paracetamol or NSAIDs as acute treatment.
Cluster Headaches
Recurrent bouts of acute, unilateral pain, centred over eye, temple or forehead. Pain very severe and tends to be relieved by physical activity. Autonomic features often accompany headache (e.g. nasal congestion, watering / redness of eye).
Cluster headache can be classified as:
• Episodic: headache free periods > one month (90%)
• Chronic: headache free periods < one month (10%)
Management: oxygen and subcutaneous / nasal triptan may benefit acute attacks. Verapamil can be beneficial prophylactically.
What is NF1?
NF1: von Recklinghausen disease (chromosome 17): incidence 1 in 3000.
2 or more of:
o Café-au-lait spots: >6 flat pigmented macules (>5mm pre-puberty or >15mm post-puberty)
o Axillary / inguinal freckling
o Bony lesions e.g. sphenoid dysplasia or osteoarthritis
o >2 neurofibroma tumours or 1 plexiform neurofibroma (larger, more extensive) – both are cutaneous tumours
o First degree relative NF1
o ≥2 iris harmatomas (Lisch nodules) – benign tumours only seen on slit lamp
o Optic nerve glioma
What is NF2?
Chromosome 22: incidence 1 in 25,000. Café-au-lait macules + skin neurofibromas rarely found in NF2. Typically presents with hearing loss or CNS tumours. Bilateral acoustic neuroma is pathognomonic.
Those with probable diagnosis must have:
• Family history of NF2 AND either:
• one unilateral acoustic neuroma
• any two of: meningioma, glioma schwannoma, juvenile posterior subcapsular lenticular opacities / juvenile cortical cataracts
Management and prognosis of neurofibromatosis?
No cure – many have such mild symptoms that they do not present. Management involves early identification of complications.
MRI determines site + delineates invasion of tumours in eyes, bones, nerve, brain
Eye tests: annual ophthalmology examinations important to detect eye signs early
BP monitoring: may develop HTN secondary to renal artery stenosis or pheochromocytoma
Genetics: testing and counselling may be necessary
Removal of neurofibromas: laser technology or surgical resection – medical treatment may be considered in unresectable or metastatic lesions
Prognosis: NF1 ~ 8 year reduced mortality(?) mainly due to hypertension, spinal cord lesions & malignancy. NF2 also significant rates of mortality and morbidity.
What is tuberous sclerosis?
Autosomal dominant: non-malignant tumours in multiple organs – primarily skin, brain, heart, kidney, eye or bone.
Prevalence 1 in 9000 births. Wide range of manifestations in same family: spontaneous mutations ~2/3rds cases. Younger presentation = higher risk of intellectual disability
Classic features:
• Ash leaf macules: depigmented patches of skin which fluoresce under UV light
- Angiofibromata: sebaceous adenoma in butterfly distribution over nose + cheeks after 3 years of age
- Shagreen patches: roughened skin patches over lumbar spine
- Subungual fibromata: fibromata beneath nails
- Fibrous plaques: on forehead / temple
- Brain lesions: epilepsy (85% and 70% in first year of life, infantile spasms in 30%), cognitive impairment, autism, neuropsychiatric issues (e.g. severe anxiety).
Additional features may include brain tumours, rhabdomyoma of the heart, cystic / fibrous change in the lungs and polycystic kidney disease
Investigations and management of tuberous sclerosis?
- Genetic testing (TSC1 or TSC2 mutations sufficient for diagnosis).
- MRI / CT (cortical / subcortical tubers, subependymal nodules, neuronal migration defects, subependymal giant cell astrocytomas)
- EEG (seizures)
- Abdo MRI (renal involvement, angiomyolipoma, renal cysts)
- ECHO (atrial myxoma)
- ECG, BP, ophthalmological exam (retinal hamartomas).
- Dental + skin exam (e.g. facial angiofibroma, tooth enamel defects).
Management:
- laser therapy (removes angiofibromas)
- BP control
- dialysis (if renal failure)
- lung monitoring (women >18 years may develop lymphangioleiomyomatosis of lungs – involves cyst formation in lungs, therefore, CT lungs to identify pathology early)
- mTOR inhibitors (protein kinase that controls cell growth and proliferation therefore inhibiting it can reduce non-malignant tumour growth – may be used in individuals with subependymal giant cell astrocytomas, renal angiomyolipomas and lymphangioleiomyomatosis).
What is Sturge-Webber syndrome? (SWS)
Sporadic vascular disease, 1 in 50,000 livebirths,
Abnormal skin vessels: port-wine stain covering at least V1 division, may also cover lower face, trunk + oral muscosa
Abnormal brain vessels: leptomeningeal angiomas (benign vascular tumours), can lead to seizures – typically focal and on opposite side of port wine stain. Other neurological abnormalities: cognitive impairment, hemiparesis, headache & developmental delay
Abnormal eye vessels: can lead to glaucoma + buphthalmos
Investigations and management of SWS?
Cranial contrast MRI: white matter abnormalities, cerebral atrophy + leptomeningeal angiomatosis. Calcification of gyri may also be noted, but more apparent on CT.
Management: control seizures (hemispherectomy or lobectomy in intractable cases). Monitor for complications e.g. glaucoma + consider of laser therapy for port wine stains.
What is Von Hippel-Lindau disease (VHL)?
Multi-organ autosomal dominant – tumour suppressor gene. Incidence 1 in 30,000. Cerebellar haemangiomas, retinal angiomas, cystic lesions in kidney, pancreas and epididymis also associated with the condition. Renal carcinoma = most common cause of death.
Regular renal+ brain imaging required for early identification of cysts or masses. Dialysis may be required for kidney failure, pancreatic enzyme supplementation for severe pancreatic disease may be necessary.
