Category Archives: Neurology

Muscular Dystrophy

General paediatrics, Neurology

Dystrophin is largest gene in body – prone to duplications/deletions. Large errors can be picked up quickly on testing. Point mutations (30%) take more sequencing work.

Duchenne MD is X-linked but girls can get symptoms (or develop later dilated cardiomyopathy) due to lyonisation.

Life expectancy was 18-20 yrs but now with steroids and non-invasive ventilation, 40 plus.

Different natural history trajectories identified – makes trials hard, as not comparable…

Becker muscular dystrophy is similar but less severe. Other muscular dystrophies include myotonic dystrophy, Emery-Dreifuss muscular dystrophy, facioscapulohumeral muscular dystrophy, limb-girdle muscular dystrophies, and congenital muscular dystrophies. Spinal muscular atrophy related. Management of all similar.

Diagnosis

Often delayed (average 2.5 years after onset of symptoms), especially if there are developmental issues that perhaps distract from the motor delay problem (mean age 6.6 years if developmental issues, cf 4.9 years if not). Classically delayed motor milestones, frequent falls, abnormal gait, muscle pain; but sometimes speech and language delay, learning difficulty more prominent. Urine/bowel issues. Later difficulty with jumping, running, climbing steps, and rising from the floor.

Leg flexors tend to stay strong cf extensors – leads to lordosis and contractures, and classic posture where weight forward to avoid jack knifing.

Calf hypertrophy classic. Tone and reflexes reduced (cf cerebral palsy).

Gower’s sign – using hands/arms to get up from floor and to standing position

Creatine kinase levels are elevated. Diagnosis is confirmed by genetic testing.

If CK normal, then EMG and muscle biopsy required.

Treatment

Lung function should be monitored.

Steroids are recommended from diagnosis. Preserves ambulation, respiratory function (delays the need for mechanical ventilation); avoids/delays scoliosis surgery; delays onset of cardiomyopathy; increased survival.

ACE inhibitors recommended to delay onset of cardiomyopathy.

Gene therapy difficult because of size of gene and problem of packing into vector!

Lots of trials. Givinostat approved by FDA – old drug for JIA! – conditional license in UK, early access programme in UK. Vamorolone is steroid, potent but less side effects eg bone/growth – now recommended by NICE (January 2025).

FDA has approved first gene therapy treatment – but have been fatalities and effect over time unclear.

Ataluren – oral – but EMA have withdrawn license due to poor efficacy.

Family Support

Muscular Dystrophy UK

[Zoya Al-Haswani – Heartlands Hospital]

Stroke in children

Emergency medicine, General paediatrics, Neurology

Rare but happens.

Differential:

Can be due to arterial or venous occlusion.  50:50 in kids cf adults (80% infarct). Haemorrhagic can be due to rupture into infarct.

Presents with focal signs, headache, seizures most commonly. Else dysphasia, vomiting!, confusion. Fever! Acute signs often lacking or fluctuant cf history!  FAST criteria only 78% sensitive. 

NIH stroke severity scale has paeds version. 

Risk factors

Black/Asian

Cardiac (esp surgery, right to left shunt)

Sickle cell – esp anaemia, acute chest syndrome, HbS or HbS/Beta thal

Thrombophilia

Liver/kidney disease (secondary prothrombotic tendency)

VZV within 1yr, enteroviruses, HIV.

Vasculitis – Moya Moya (peaks at 5-9yr else adulthood), SLE, other

Cocaine, glue.

Marfans, homocysteinuria, Fabry’s disease, Neurofibromatosis

Cancer, radiotherapy

Hypoglycaemia. 

Management

High flow O2, 10ml/kg saline 

Imaging within 1hr. 

BP – avoid high and low? Cf adults

Monitor for RICP

Treat with aspirin.

Tests

  • CTA/MRA at time of CT/MRI
  • Echo
  • (Transcranial doppler in sickle cell- via temporal bony window)
  • Hbopathy screen
  • Cholesterol
  • Lupus anticoagulant, Anti cardiolipin ab (ACLA), consider beta 2GP1
  • Homocysteine
  • Alpha galactosidase
  • Lipoprotein A – a kind of LDL but induces vascular inflammation, so a marker for CVS disease 
[RCPCH guideline May 2017]

Hypokalaemia

Clinical, General paediatrics, Neurology, Renal

Could be reduced intake but usually excessive losses –

RenalNon-renal
Renal tubular acidosis (type 1 or 2)Vomiting eg pyloric stenosis
Bartters or Gitelmans syndromeDiarrhoea
DiureticsLaxative overuse
Hyperaldosteronism (CAH, tumour)Thyrotoxicosis
Salbutamol
Familial periodic paralysis
Pseudo-Bartter’s
Trauma
Diabetic ketoacidosis

Symptoms depend on severity and how rapidly decrease has happened. Chronic low levels are better tolerated. Since potassium important for membrane potentials, effects are mostly neuromuscular.

  • Cramps, weakness, paralysis
  • Ileus
  • Metabolic acidosis (although underlying cause often produces alkalosis)
  • Arrhythmia, heart failure
  • Rhabdomyolysis

ECG classically shows U waves, T wave flattening, and ST-segment changes. Can be tall wide P waves, can look like long QT if T and U waves merge.

Do urine and blood electrolytes to look at fractional excretion.

[Endocrine connections 2018][Current Treatment Options in Peds 2022]

Rett Syndrome

General paediatrics, Genetics, Neurology

Exclusively females (lethal in males? Or rate of germ cell mutations higher in male germ cells?).  Virtually always sporadic – so not exactly X linked dominant.

MECP2 gene on X chromosome.

Developmental arrest at 6-18 months, then regression, loss of speech, stereotypies esp hands.

Often epilepsy, then complications of severe neurodisability eg chronic lung issues.

Not degenerative however – can live into middle life.

Focal epilepsy

General paediatrics, Neurology

As opposed to generalized epilepsy. Potentially associated with a brain lesion (congenital or acquired), but not always. EEG will usually confirm.

Associated with prolonged or focal febrile convulsion – chicken or egg?

See:

Temporal lobe epilepsy

The most common focal epilepsy.  Sense of déjà vu, phantom smells, panic attacks as possible aura symptoms! Talking gibberish, lip smacking, staring, posturing are more obvious.

Treatment

Levetiracetam or Lamotrigine first line, the former (Keppra) can be loaded more quickly though.

Honey in medicine

Allergy, General paediatrics, Infectious disease, Neurology, Nutrition

Contains a range of different sugars, aromatic oils, also pollens and bee proteins. Royal jelly and beeswax related, of course.

High fructose content can cause GI intolerance in some.

Allergic reactions can happen, often unrecognised, mostly due to specific pollens (depending on what flowers the bees feed on), in minority to bee proteins. Commercial honey tends to contain v low amounts of pollen, due to production techniques. IgE test for honey is available, but you may need to skin prick test with the specific honey if negative.

Honey eaten all year round is rumoured to prevent hay fever symptoms because of the pollens it contains, but this has not been proven, although it’s a nice idea related to immunotherapy. Depends on getting the right pollens of course – bees don’t like grass and birch flowers, probably. In some it may just trigger allergy symptoms.

Cross reaction between honey and bee venom is reported, not surprisingly, but not automatic.

Plant toxins can be present in sufficient quantities in honey to cause poisoning eg rhododendrons (some species).

Botulism reported in infants – failure to thrive, hypotonia, cranial nerve palsies. Clostridium and other bacteria cannot grow in honey due to the high sugar content, but spores can be present. So advice is not to give honey to infants.

Dravet syndrome

General paediatrics, Genetics, Neurology

Previously Severe myoclonic epilepsy of infancy. Charlotte Dravet described in 70s. Characterised by:

  • Refractory epilepsy
  • Onset in infancy
  • Associated neurodevelopmental problems

Due to defect in SCN1A gene on chromosome 2q24 (a sodium channel), usually de novo. Many mutations, don’t predict severity, unfortunately.

Accounts for about 7% of epilepsy presenting in first 3 years of life.

Onset around 5-8 months, often with febrile illness so can look like typical febrile convulsion. But often prolonged. Neurodevelopmental problems come later…

Later though, multiple seizure types. Hypotonia, ataxia, spasticity all seen. Dysautomnia can be a feature. ADHD and autistic traits common later.

EEG can be normal, or vary over time, with multifocal or generalised changes, photosensitivity too.