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Flashcards in Neurology Deck (124):

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?

- First degree relatives with NF-2 confirmed
- Any of the following:
   >> Neurofibroma
   >> Meningioma 
   >> Glioma 
   >> Schwannoma


- 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

- 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
- 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?

- Migraine with aura
- Migraine without aura
- Tension-type headache
- Cluster headache

- 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?

1. Acute
2. Acute-recurrent
3. Chronic non-progressive
4. 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

- 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

- 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

- 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?


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?

- WBC: 0-30
- Neutrophil %: 2-3
- RBC: 0-2
- Glucose: 30-120 mg/dL
- Protein: 20-150 mg/dL

- 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?

- Brian abscess
- Subdural empyema/effusion
- Disseminated infection
   >> Osteomyelitis
   >> Septic arthritis
   >> Abscesses
- Shock/DIC (disseminated intravascular coagulopathy)
   >> Meningococcemia!

- 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 cerebral aqueduct stenosis
- Secondary gliosis from congenital infection
- Dandy-Walker malformation
- Arnold-Chiari malformation
- Myelomeningocele
- Craniosynotosis

- 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?


- 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

A image thumb

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

- Peripheral neuropathy
- Headache
- Nystagmus
- Sedation

- Nausea and vomiting
- Constipation


What are the side effects of valproate?

- Alopecia
- Thrombocytopenia
- Tremor
- Hypothermia

- Headache
- Somnolence
- Diplopia
- Encephalopathy

- Nausea and vomiting
- Diarrhea
- Hepatic failure
- Pancreatitis


How is the prognosis for West syndrome?


- 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 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 management for juvenile myoclonic epilepsy?

Life-long treatment of AEDs
- Valproate (1st line)
- Lamotrigine
- Topiramate
- Levetiracetam
- Benzodiazepines


How is the prognosis for juvenile myoclonic epilepsy?


- Good control with life-long valproate
- Minimal effect on development due to later onset


What is the typical EEG pattern for infantile spasms?

Hypsarrhythmia (VF) in inter-ictal EEG


What is the typical EEG pattern for absence seizures/childhood absence epilepsy?

Generalized 3/second spike and wave discharge (VT)

A image thumb

What are the presenting features of childhood absence epilepsy?

Age of onset: 4-12 years (peak at 6-7 years)

Types of seizure
- Absence seizure
- Can be induced by hyperventilation


What is the management for childhood absence epilepsy?

- Valproate
- Ethosuximide

>> Avoid carbamazepine and phenytoin as they may precipitate absence seizures


What are the presenting features of benign childhood epilepsy with centrotemporal spikes (BCECTS) or benign Rolandic seizures?

Age of onset: 4-10 years

Types of seizure
- Simple partial seizure involving the tongue, mouth, face and upper extremities
- Usually at sleep-wake transitions
- Generalized tonic-clonic seizures IN SLEEP


What is the typical EEG pattern for benign Rolandic seizures?

Repetitive spikes in centrotemporal area with normal background


What is the management for benign Rolandic seizures?

No medication is necessary if seizures are infrequent

Frequent seizures requiring AED:
- Carbamazepine
- Valproate
- Gabapentin


How is the prognosis for benign Rolandic seizures/BCECTS?


- ~15% of all childhood seizures (non-febrile seizures)
- Remission in adolescence in almost all cases


Name the age of onset of the following common seizure syndromes of childhood:

1. West syndrome/infantile spasms
2. Lennox-Gastaut syndrome
3. Benign Rolandic epilepsy
4. Panayiotopoulos type, early onset benign childhood occipital epilepsy
5. Gastaut type, benign childhood occipital epilepsy
6. Childhood absence epilepsy
7. Juvenile myoclonic epilepsy

1. 4-8 months
2. 1-7 years (peak 3-5 years)
3. 4-10 years
4. 1-14 years (peak 5. 3-16 years (peak 8-9 years)
6. 4-12 years (peak 6-7 years)
7. Adolescence to adulthood (peak 12-16 years)


Name the 2 epileptic syndromes associated with nocturnal seizures/seizures during sleep.

Panayiotopoulos type of benign childhood early-onset occipital epilepsy - nocturnal seizures of vomiting and eye deviation +/- visual symptoms

Benign Rolandic seizures: associated with GTC during sleep


What is the definition of status epilepticus?

Seizures lasting for more than 30 minutes from which the patient does not regain consciousness


What is the management of status epilepticus?

5 minutes: PR diazepam/IM buccal midazolam
--> try to achieve IV access as soon as possible

5-20 minutes/once IV access achieved: IV lorazepam 0.1mg/kg or IV diazepam 0.3mg/kg

>20 minutes: IV phenytoin in >2 years; IV phenobarbital in <2 years
                        > Also pentobarbitone/thiopentone


What is the definition of refractory status epilepticus?

Failure to respond to 2-3 AEDs in combination with seizure duration of at least 60 minutes


How do we manage a convulsing child upon admission to AED?

- Confirm ABC and resuscitate as necessary
- Achieve IV access as soon as possible
- Check Hmstix for hyper/hypoglycemia and treat glucose imbalance if abnormal
- Terminate seizure with AED if still convulsing
   >> PR diazepam
   >> Buccal midazolam
   >> IV lorazepam: first choice if IV access attained
   >> IV diazepam
   >> IV phenobarbitone: >2 years of age
   >> IV phenytoin: >2 years of age
   >> General anesthesia/pentobarbitone/thiopentone if all above fail


What are the possible complications of status epilepticus?

Cerebral complications
- Hypoxia
- Cerebral edema
- Raised intracranial pressure
- Cerebral venous thrombosis
- Cerebral infarction

Cardiopulmonary complications
- Hypotension
- Hypertension
- Arrhythmia
- Cardiac failure
- Respiratory failure
- Aspiration

Metabolic complications
- Hyperpyrexia
- Dehydration
- Electrolyte disturbances
- Lactic acidosis
- Rhabdomyolysis

- Acute renal failure
- Acute hepatic failure
- Fractures
- Disseminated intravascular coagulopathy


Patients with which kind of brain lesion are best candidates for epileptic surgery?

Mesangial temporal sclerosis


What is acute disseminated encephalomyelitis?

Immune-mediated inflammatory disorder of the CNS associated with widespread demyelination affecting the white matter of the brain and spinal cord PRECEDED BY A VIRAL INFECTION OR VACCINATION

If long-term/chronic, think multiple sclerosis or neuromyelitis optica


What are the possible presenting features of ADEM (acute disseminated encephalomyelitis)?

- Headache
- Nausea and vomiting
- Pyrexia
- Malaise

- Rapid onset of encephalopathy with multifocal deficits
- Seizures
- Motor: cerebellar ataxia, pyramidal syndrome
- Brainstem involvement


What are the possible investigation findings of ADEM?

LP: variable pleocytosis with oligoclonal bands

MRI: large, multifocal, poorly-marginated regions of demyelination affecting bilateral white matter and deep grey matter (basal ganglia, thalamus)


What is the management plan for ADEM?

- Supportive treatment
- High-dose corticosteroids

>> Prognosis favourable


What is the definition of cerebral palsy?

Abnormality of movement and posture, causing activity limitation, attributed to non-progressive disturbances that occurred in the developing fetal or infant brain

>> Usually for brain injuries up to 2 years of age
>> After an acquired brain injury


What is the most common cause of motor impairment in children?

Cerebral palsy (2 per 1000 live births)


What are the four types of cerebral palsy?

- Spastic
   >> Diplegic
   >> Hemiplegic
   >> Quadriplegic
- Dyskinetic
   >> Choreoathetoid
   >> Dystonic
- Ataxic
- Mixed


What are the possible causes of hypotonia in a baby?

Central (Cerebral and spinal)
- Antenatal/Genetic
   >> Chromosomal
         :: Down's syndrome
         :: Prader-Willi syndrome
         :: Fragile X syndrome
   >> Congenital infections
         :: Toxoplasmosis
         :: Rubella
         :: CMV
         :: Herpes
         :: Syphilis
   >> Congenital CNS malformations
- Perinatal/Postnatal
   >> Birth asphyxia
   >> Intracranial hemorrhage
   >> Metabolic causes
         :: Symptomatic hypoglycemia
         :: Kernicterus
         :: Hypocalcemia
   >> Endocrine causes
         :: Hypothyroidism
         :: Hypopituitarism

- Motor neuron/anterior horn cell
   >> Spinal muscular atrophy
   >> Polio
- Peripheral nerve
   >> Charcot-Marie-Tooth syndrome
   >> Drugs: phenytoin, isoniazid
- Neuromuscular junction
   >> Congenital myasthenia gravis
- Muscle
   >> Myopathy
         :: Congenital
         :: Metabolic
             ~ Glycogen storage
             ~ Lipid metabolism
             ~ Inflammatory: dermatomyositis
   >> Muscular dystrophy
   >> Dystrophy myotonica
   >> Mitochondrial diseases


What are the causes of hypotonia that respond rapidly to treatment/are easily reversible?

- Infection
- Intracranial bleeding
- Hydrocephalus
- Metabolic causes: hypoglycemia
- Electrolyte disturbances: hypokalemia, acidemia, hypermagnesemia
- Iatrogenic: drugs and toxins
- Seizures


What is the most common cause of neuromuscular disease in children?

Duchenne muscular dystrophy


What is the second most common cause of neuromuscular disease in children?

Spinal muscular atrophy


What are the presenting features of Werdnig-Hoffman disease/Type I spinal muscular atrophy/SMA?

Antenatal: decreased fetal movements

At birth: arthrogryposis

- Lack of antigravity power in hip flexors
- Extended posture
- Intercostal recession with bell-shaped torso
- Paradoxical breathing
- Signs of hypotonia: slips under armpits, inverted U sign, scarf sign, knee-ear sign
- Absent deep tendon reflexes


The baby never sits up without support


What is the prognosis for Werdnig-Hoffman disease/Type I SMA?


- Death from respiratory failure within 12 months


What is arthrogryposis?

Positional deformities of the limbs with contractures of at least two joints


Which gene is affected in spinal muscular atrophy?

SMN-1 and SMN-2 genes at chromosome 5 (5q13)


What is the mode of inheritance of spinal muscular atrophy?

Autosomal recessive


What is the pattern of muscular atrophy/wasting for peripheral neuropathies?


>> Proximal for muscular diseases


What will be seen on nerve biopsy in a patient with Charcot-Marie-Tooth disease?

"Onion-bulb formation" due to hypertrophic nerves by attempts of remyelination


What are the presenting features of Charcot-Marie-Tooth disease?

- Distal atrophy in legs more than arms: champagne legs
- Pes cavus
- Rare sensory loss distally with hyporeflexia


What is the mode of inheritance of Charcot-Marie-Tooth disease?

Mostly autosomal dominant


What is the typical clinical course of Guillan-Barre syndrome?

Usually 2-3 weeks after URTI or campylobacter gastroenteritis

- Ascending symmetric muscle weakness
- Areflexia
- Autonomic involvement
- Distal sensory symptoms rare
- Risk of aspiration if bulbar muscles are affected
- Risk of respiratory depression if respiratory muscles are affected


Maximum muscle weakness at 2-4 weeks after onset
Full recovery in 95% but takes up to 2 years


What is the CSF profile for GBS?

CSF protein markedly raised but may not be seen until the second week of illness


What is the management for GBS


- Steroids have NO beneficial effect


What is Bell's palsy?

Isolated lower motor neuron paresis of the CNVII leading to facial weakness

- HSV post-infection (more in adults)
- Hypertension: significant association between Bell's palsy and sarcoidosis


What is the major complication of Bell's palsy?

Conjunctival infection due to incomplete eye closure on blinking


What are the possible differential diagnoses for Bell's palsy?

- Compression at the cerebellopontine angle, especially if CNVIII is involved
- Bilateral: sarcoidosis, Lyme disease


What are the common presenting features of juvenile myasthenia?

Usually after 10 years of age

- Ophthalmoplegia
- Ptosis
- Myopathic facies: loss of facial expression
- Difficulty in chewing
- Proximal muscle weakness

>> Shakes hands with mom for weakness of mother (X-linked?)


How can we diagnose juvenile myasthenia?

- Improvement following administration of IV edrophonium
- Positive acetylcholine receptor antibioties (60-80%)
- Anti-muscle-specific kinase antibodies (anti-MuSK)


What is the management of juvenile myasthenia?

- Anti-muscarinic drugs: neostigmine, pyridostigmine
- Steroids: predinosolone
- Immunosuppressants: azathioprine

Crises: plasma exchange

Thymectomy if:
- Thymoma present
- Response to medical therapy unsatisfactory


What is the mode of inheritance of Duchenne muscular dystrophy?

X-linked recessive (1/3rd: sporadic)

>> Deletion at Xp21 site -- dystrophin


What is the average age of diagnosis of Duchenne muscular dystrophy (DMD)?

5.5 years -- the child is normal at birth


What are the presenting features of DMD?

- Language and/or motor delay
- Waddling gait
- Gower's sign: need to turn prone to rise
- Calf pseudohypertrophy: replacement of muscle by fat and fibrous tissue
- Hyporeflexia


What is the prognosis of DMD?


- No longer ambulant by 10-14 years
- Life expectancy: late twenties
- Cause of death
   >> Respiratory failure
   >> Cardiomyopathy


What is the pathophysiology of DMD?

Missing dystrophin >> fragile muscle fibres >> muscle fibre breakdown >> necrosis and regeneration


What investigations are useful to help diagnose DMD?

- LFT: elevated transaminase
- CK/CPK: elevated (50-100 times)
- LDH: elevated (CK = CPK...)

Electromyography (EMG)

Muscle biopsy

Genetic studies: molecular genetic studies for mutations of the DMD1 gene


What are the complications of DMD?

- Flexion contractures
- Scoliosis
- Osteopenia of immobility
- Pathological fractures
- Respiratory failure and cardiomyopathy


What is the management plan for DMD?


- OT and PT
- Bone and cardiac health monitoring
- Vitamin D and bisphosphonates for bone health
- Steroids: prednisone, deflazacort
- Surgical: scoliosis, contracture release
- Gene therapy: trials underway


What is Becker muscular dystrophy?

Some functional dystrophin produced
- less severe than DMD


What is the prognosis/clinical course for Becker muscular dystrophy?

Age of onset: 11 years

- Inability to walk: late twenties
- Life expectancy: late forties - normal


What are the presenting features of dermatomyositis?

1. Symmetric proximal muscle weakness: progressive over weeks/months
2. Elevated muscle enzymes: CK, aldolase, AST, ALT, LDH
3. EMG changes: high frequency repetitive discharge
4. Muscle biopsy: inflammatory infiltrate and atrophy
5. Typical rash of dermatomyositis
     - Gottron's papules
     - Gottron's sign
     - Heliotrope rash
     - Shawl sign
     - Mechanic hands
     - Periungal erythema


What are the systemic complications/features of dermatomyositis?

- Conduction defects and arrhythmia
- Ventricular hypertrophy
- Congestive heart failure
- Pericarditis

- Respiratory muscle weakness
- Interstitial lung disease
- Aspiration pneumonia

- Dysphagia
- Swallowing problems if pharyngeal muscles involved

Increased risk for malignancies
- Breast
- Ovarian
- Lung
- Colon


What is the management plan for dermatomyositis?

- Physiotherapy/occupational therapy
- Drugs
   >> High dose steroids and taper
   >> Immunosuppressants: MTX, azathioprine, cyclosporin
   >> IVIG
   >> Hydroxychloroquine for rash
- Malignancy monitoring/surveillance


What is the typical age of onset for dermatomyositis?

5-10 years


What is the mode of inheritance of dystrophia myotonica?

Autosomal dominant: nucleotide triplet repeat expansion

>> Always examine mother for myotonia as well
      - Slow release of handshake
      - Difficulty releasing the tightly clasped first


What are the systemic involvements of dystrophia myotonica?

- Cataracts and retinal degeneration in adults
- Baldness and testicular atrophy in males
- Infertility
- Diabetes
- Conduction defects of the heart (90%)
    >> First degree heart block
    >> Atrial arrhythmias
- Cardiomyopathy: major cause of death


What is the major cause of death in dystrophia myotonica?



What are the presenting features of dystrophia myotonica?

- Ptoisis
- Bifacial weakness
- Frontal baldness
- Myopathic facies
- DISTAL muscular weakness in contrast to other myopathies
- Stepping gait
- Myotonia: delayed relaxation of muscles after exertion


What is the management for dystrophia myotonica?

- No cure
- Phenytoin for myotonia


What is the mode of inheritance of Friedreich ataxia?

Autosomal recessive
- Trinucleotide repeat disorder


What are the presenting features of Friedreich ataxia?

- Worsening ataxia
- Distal wasting of legs
- LL areflexia with up-going plantar response
- Pes cavus
- Dysarthria

>> DDx: similar to Charcot-Marie-Tooth

In Frederich ataxia, there is:
- Abnormal propioception
- Upgoing plantar response
- Optic atrophy


What are the complications of Friedreich ataxia?

- Kyphoscoliosis
- Cardiomyopathy
- Death at 40-50 years due to cardiorespiratory compromise


What is the mode of inheritance of ataxia telangiectasia?

Autosomal recessive -- DNA repair disorder


What are the presenting features of ataxia telangiectasia?

- Motor developmental delay
- Oculomotor problems: incoordinated ocular pursuit of objects -- oculomotor dyspraxia
- Difficulty with balance and coordination
- Telangiectasia ~4 years of age
   >> Conjunctiva
   >> Neck
   >> Shoulders
- Increased susceptibility to infection: IgA surface antibody defect
- Increased risk for ALL (~10%)
- Raised AFP (alpha-fetoprotein)


What is the typical age of onset for Freidreich's ataxia?

8-15 years


What is MELAS?

- Myoclonic Epilepsy
- Lactic Acidosis
- Stroke-like episodes


Name four common neural tube defects.

1. Anencephaly
2. Encephalocele
3. Spina bifida
4. Meningocele, myelomeningocele


What eye disease is Sturge-Weber disease associated with?