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Alterations in cardiac depolarisation and repolarisation are reported in 74% of patients with cerebrovascular events.1 They are more frequent after subarachnoid and intracerebral haemorrhage, but may also occur in acute ischaemic stroke (15–30%) and are related to an increased incidence of malignant arrhythmia and sudden death (6%).2
The most common ECG alterations are QT prolongation, ST segment alterations, T wave flattening or inversion, and abnormal U waves.1 ECG changes may be similar to those commonly observed in patients with coronary artery disease,2 but they have also been demonstrated in the absence of autopsy proven heart disease.1 This suggests a neurogenic rather than a primary cardiac cause, mediated by unbalanced autonomic control.
Experimental evidence implicates the insular cortex in cardiovascular control and heart chronotropic organisation,2 and suggests its involvement in the genesis of adverse neurogenic ECG alterations.
A 68 year old right handed female was admitted after the acute onset of mild right ataxic hemiparesis, right facial and hypoglossal nerve palsy, and dysarthria. The patient was vegetarian, had no history of diabetes or cardiac disease, and was a non-smoker without relevant family history. Blood pressure was 150/100 mm Hg and heart rate (HR) was 94 beats per minute (bpm). The admission brain CT and Doppler ultrasounds were normal. A left anterior hemiblock was detected at ECG (fig 1C).
Standard blood chemistry showed macrocytic anaemia, with other parameters within normal range, including serum lipids (lipoprotein a, total, HDL, and LDL cholesterol, and triglycerides). Antithrombin III, PT, PTT, fibrinogen, protein C and S activity, and activated protein C resistance were normal. Searches for lupus anticoagulant, antinuclear antibodies, antibodies to extractable nuclear antigens, anti-neutrophil cytoplasm autoantibodies, anticardiolipin antibodies, and cryoglobulins were negative.
A homocysteine serum level of 35.7 μmol/l (normal values: <20 μmol/l), vitamin B12 deficiency (90 pg/ml; normal values: 200–1000 pg/ml), and normal folic acid were detected. Vitamin B12 and antiplatelet therapy were started. The patient’s clinical condition improved and 5 days later she was discharged.
The day after discharge she was readmitted because of the recurrence of moderate right ataxic hemiparesis, dysarthria, and non-fluent aphasia with phonemic paraphasia, anomia, and with essentially preserved comprehension and repetition. Blood pressure was 130/90 mm Hg and HR was 92 bpm. Blood examination showed the previously detected macrocytic anaemia, and a C reactive protein (CRP) value of 2.14 mg/dl (normal value: <0.8 mg/dl). Brain CT and MRI (fig 1A and B) showed an infarct limited to the left insular cortex with no other lesions on the diffusion weighted images.
The admission ECG showed a global T wave inversion (fig 1D), which persisted on subsequent monitoring, and disappeared only after 2 months. No other ECG alterations were detected, including QT prolongation (QT = 0.34; QTc = 0.42 s). The patient had no cardiac symptoms and transthoracic echocardiography was normal as was serum potassium, calcium, and cardiac enzyme (creatine kinase-MB, troponine I, and myoglobin) investigation repeated over 5 days.
Following 3 weeks of therapy, vitamin B12 and homocysteine levels were normal, CRP value was 1.87 mg/dl, and the macrocytic anaemia had improved.
By 2 months after the cerebrovascular events, macrocytic anaemia was absent, homocysteine, vitamin B12, and CRP were normal, and the ECG had nearly normalised. An adenosine-thallium scan performed 6 months after stroke onset showed no evidence of coronary artery disease. To date there have been no cardiac events.
Acute insular stroke may present with various clinical presentations, due to the anatomic and functional complexity of the insular lobe and its wide connections with the frontal, temporal, parietal, and olfactory cortex, and with the basal ganglia, thalamus, and limbic structures.3,4 It is an important gustatory, somatosensory, and visceral motor sensory processing area, a component of the vestibular and limbic cortex, and is implicated in pain processing, volitional swallowing, cardiovascular control, and cerebrogenic sudden death.2–4
Pure insular strokes, rare entities in clinical practice, are defined as infarcts restricted to the insula in which coexisting brain lesions are exclusion criteria, with the exception of some involvement of the claustrum and capsula extrema.4 This definition is justified by the complex insular arterial supply which principally supplies the insular cortex, the capsula extrema, and the claustrum, and, sporadically, the capsula externa.4
The prominent clinical features of our case were neuropsychological disorders (expressive aphasia, dysarthria, verbal memory impairment), and electrocardiographic alterations, represented by persistent T wave inversion.
Neurogenic ECG alterations are often transient, but cause diagnostic problems, mimicking acute myocardial infarction. Some features of T waves may be suggestive of heart pathology, but they are non-specific, making it important to consider a neurogenic genesis to avoid unsuitable therapies.
The neurogenic nature of T wave inversion in our case was demonstrated by the lack of evidence of coronary artery disease or cardiac pathology, both of which were ruled out by echocardiography and adenosine-thallium scan. Myocardial enzymes, which have also been reported to be elevated mainly in large size stroke, were normal probably because of the limited extent of cerebral infarction.
In insular stroke the pathophysiology of abnormalities of rate, rhythm, and conduction is related to an imbalance of autonomic cardiovascular control and to increased circulating and local myocardial tissue catecholamines, suggesting an underlying sympathetically mediated mechanism. The insular cortex has been shown experimentally to contain an arrhythmogenic centre implicated in neurogenic electrocardiographic changes.2
There is evidence of cortical asymmetry in the regulation of cardiovascular functions: the left insula is concerned mainly with control of parasympathetic cardiac drive, and the right with control of cardiovascular sympathetic tone.1,2 Damage to the left insular cortex by stroke may shift sympathovagal balance towards increased basal sympathetic tone (a pro-arrhythmic condition), with a decrease in the randomness of HR variability, and may contribute to the excess cardiac mortality following stroke.1,2
Insular infarcts so far reported are caused by artery to artery or cardiac embolisms.4 To our knowledge this is the first reported case of insular stroke associated with hyperhomocysteinaemia, which is an emerging independent risk factor for stroke and for vascular recurrence after ischaemic stroke.5
In conclusion, persistent neurogenic T wave alteration due to a left insular infarct associated with hyperhomocysteinaemia is reported in this paper. The case underlines the functional complexity of the insular cortex, its role in the generation of cardiovascular changes, and the importance of cardiac monitoring in stroke patients.
Competing interests: none declared
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