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Immaturity of medullary cardiorespiratory neurones leading to inappropriate autonomic reactions as a likely cause of sudden death in Rett’s syndrome
  1. P O O JULU,
  2. A M KERR


  3. S HANSEN,
  5. G A JAMAL
  1. Peripheral Nerve and Autonomic Unit, INS
  2. Southern General Hospital, Glasgow G51 4TF and
  3. *Glasgow University Department of Psychological Medicine
  4. Gartnavel Royal Hospital, Glasgow, Scotland

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    Editor,—Rett’s syndrome is a cause of intellectual disability with frequent respiratory dysrhythmia. In a survey in Great Britain, we identified episodic hyperventilation in 75%, apnoeic attacks in 70%, non-seizure vacant spells in 77%, and epileptic seizures in 70% of 191 classic cases. Of all reported deaths from Rett’s syndrome, 25% were sudden and unexpected. Certain groups of interacting neurones in the medulla perform autonomic and respiratory functions that can be measured non-invasively. With informed consent and the approval of the local ethics committee, we measured the autonomic reactions to hyperventilation in Rett’s syndrome and age matched controls while monitoring their respiration to understand the interactions between medullary autonomic and respiratory neurones.

    Breathing movements were monitored using a resistance plethysmograph tied around the chest. Sympathetic activity related to the mean arterial blood pressure (MAP)1 was measured continuously and non-invasively using the Finapres (Ohmeda). Cardiac vagal tone (CVT) was also measured continuously and non-invasively from the responses of heart rate to spontaneous baroreflex. These were converted into atropine derived units of a linear vagal scale (LVS),2 by a machine, the NeuroScope. All measurements including heart rate were integrated and stored beat-by-beat into a microcomputer.

    In eight control girls aged 4–11 years, mean (SEM) CVT was 10.5 (0.9) units in the LVS, MAP was 94.6 (6.4) mm Hg. During voluntary hyperventilation, vagal tone responded briskly and successfully corrected the raised MAP (fig 1). In six girls with Rett’s syndrome of the same age group, MAP was 78 (4.33) mm Hg during quiet rest. Vagal tone was 3.6 (0.7) units in the LVS, 65% lower than in controls (p<0.001, t test), but similar to the 3.0 (0.6) units previously reported in quiet neonates.3 During spontaneous hyperventilation, vagal tone responded briskly, but failed to correct a grossly raised MAP (fig 1). Vagal tone was invariably withdrawn at the height of sympathetic activity during hyperventilation. This sympathovagal imbalance bears the risk of cardiac arrhythmias in Rett’s syndrome, a possible cause of sudden death.

    Figure 1

    Continuous and concurrent records of mean arterial blood pressure (BP) and a measure of cardiac vagal tone expressed in units of a LVS. The upper pair of traces are examples obtained from a normal 8 year old girl to show the reaction to voluntary hyperventilation (H). The lower pair of traces are examples obtained from an 8 year old girl with Rett’s syndrome to show the reaction to her spontaneous hyperventilation (H).

    We suggest that medullary cardioinhibition is immature in Rett’s syndrome. Although neuropathological studies have shown immaturities in other areas of the brain,4 this is the first functional evidence of immaturity which is potentially useful for diagnosis and management of Rett’s syndrome.


    Finapres was purchased using Neurosciences Foundation Grant TNF 95/3.