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Of the few patients suffering from amyotrophic lateral sclerosis (ALS) that I've treated, all have also presented with systemic arterial hypertension. What is the explanation for this?
Fernando Alex de Souza, MD
This is an astute observation, and a number of reports from the literature have shown findings relevant to your question.
In 1976, a high prevalence of hypertension was reported among patients with Guamanian ALS, and an association of hypertension with ALS was found in a death certificate-based case-control study in patients from the continental United States. By contrast, in a population-based case-control study in Rochester, Minnesota, that compared 45 patients with 90 matched controls, hypertension occurred less frequently in men with ALS (4%) than in control subjects (30%; odds ratio = .10).
In 1989, a group of investigators reported a study of 9 patients with ALS and Shy-Drager syndrome whose autonomic function mediated cardiovascular regulation. Results showed subclinical sympathetic hyperfunction and parasympathetic (vagal) hypofunction that probably resulted in cardiovascular dysfunction.
Another group examined the effects of intravenous antihypertensive medications in a 49-year-old, ventilator-dependent patient with sporadic ALS. This patient had severe hypertension and tachycardia during the daytime and nocturnal hypotension without compensatory tachycardia. The patient experienced profound drops in blood pressure with relatively mild increases in heart rate. The investigators concluded that the patient's vasomotor responses indicated distinct participation of abnormally augmented sympathetic tone and especially of alpha-sympathetic hyperactivity, rather than beta-sympathetic hyperactivity, during the patient's hypertensive attacks.
Another group examined the medullary catecholaminergic neurons in 9 patients with ALS -- 5 had been on respirators and 3 had labile blood pressures (paroxysmal hypertension and nocturnal hypotension without compensatory tachycardia) -- and found that the number of tyrosine hydroxylase immunoreactive neurons in ALS was the same as in normal subjects. The researchers concluded that the lability of blood pressure in ALS probably is not related to the medullary catecholaminergic neurons.
Investigators in a study of 18 patients with early-stage ALS and 18 age-matched controls found that mean heart rate and arterial blood pressure were increased in ALS, whereas the results of standard autonomic tests were similar for ALS patients and controls. Transfer function analysis revealed reduced baroreflex sensitivity and diminished cardiorespiratory transfer during normal breathing. The study authors concluded that cardiovascular autonomic functions were intact in patients with ALS and that there was evidence of sympathetic enhancement and vagal withdrawal, which was accompanied by reduced baroreflex sensitivity. These findings are similar to those reported for essential hypertension and may point to a common central autonomic derangement in both disorders.
More recently, a review of the data from 35 consecutive ALS patients receiving riluzole, 88 randomly selected controls without ALS, and 20 patients with ALS who were not on riluzole found that 28 of the 35 ALS patients taking riluzole had elevated blood pressures as compared with 26 of 88 controls (P < .001) and 8 of the 20 ALS patients not taking riluzole (P = .007). Median systolic and diastolic blood pressures were both significantly higher (140/86 mm Hg) in riluzole-treated patients than in control patients without ALS (120/70 mmHg, P < .001). Systolic, but not diastolic, blood pressures were significantly higher in riluzole-treated patients than in controls with ALS (126 mmHg, P = .002). The investigators concluded that riluzole treatment may be associated with mild blood pressure elevations.
The data show various degrees of autonomic dysfunction in patients with ALS. On first consideration, the findings early in the disease might be attributed to shared risk factors for ALS and hypertension, such as age or smoking. However, the findings of severe autonomic dysfunction late in the disease almost certainly reflect the effects of ALS and support the possibility that ALS has a contributory role in producing changes even early in the disease course. Medullary catecholaminergic neurons appear to be spared. Baroreceptor function impairment may best account for the changes. The final report suggests that riluzole treatment may contribute to mild blood pressure elevation in patients with ALS. Although the data do not permit determining with certainty the prevalence of hypertension in patients with ALS, this prevalence is expected to change as the criteria to diagnose hypertension are expanded.
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