Cardiovascular autonomic testing in the work-up of cerebellar ataxia: insight from an observational single center study

Abstract

Background Cerebellar ataxias are a heterogeneous group of disorders of both genetic and non-genetic origin. In sporadic cases, two entities are recognized: multiple system atrophy of cerebellar type (MSA-C) and SAOA (sporadic adult-onset ataxia). The presence of severe cardiovascular autonomic failure reliably distinguishes MSA-C from other ataxias, but it may appear only late in the disease course. Objective To evaluate the diagnostic yield of cardiovascular autonomic function tests in the work-up of cerebellar ataxia. Methods We applied a cardiovascular autonomic tests battery in consecutive patients with neurodegenerative cerebellar ataxia and matched healthy controls. We recorded the presence of both orthostatic hypotension (OH) and blood pressure falls non-fulfilling the criteria of OH (non-OH BP). Sporadic cases were followed-up for an eventual conversion to MSA-C. Results Forty-two patients were recruited, 19 of whom with sporadic disease (2 probable MSA-C, 6 possible MSA-C, 11 SAOA). Sporadic and hereditary cases showed no difference concerning ataxia severity at baseline. At head-up tilt, non-OH BP falls were detected in nine patients, but not in controls. This finding was significantly more frequent in sporadic cases (p = 0.006) and was detected in five out of seven patients that during follow-up converted to possible/probable MSA-C. Findings at standing test were normal in four out of nine cases with non-OH BP falls at head-up tilt. Conclusions A complete cardiovascular autonomic battery with head-up tilt can detect early signs of BP dysregulation which may be missed at bedside tests, thus warranting its application in the first line work-up of cerebellar ataxias.

The role of cardiovascular autonomic failure in the differential diagnosis of α-synucleinopathies

“…In contrast to previous reports that milder urogenital symptoms, i.e. urinary urgency, frequency, or sexual dysfunction, already discriminate MSA from SAOA at initial presentation [75], a high prevalence of these was recently found at baseline examination of individuals with SAOA who did not convert to MSA during follow-up [76]. As early as 2007, it was shown that mild cardiac parasympathetic abnormalities may be observed in up to 58% of SAOA individuals at CAFTs [78], but no relevant orthostatic BP falls fulfilling the criteria for neurogenic OH [8].…”

“…Studies however showed that a substantial proportion of people initially labelled as SAOA may develop overt autonomic failure during the disease course, i.e. phenoconvert to MSA [75][76][77]. In contrast to previous reports that milder urogenital symptoms, i.e.…”

“…Milder falls in BP upon standing, as well as pathological cardio-vagal responses to the Valsalva manoeuver and deep breathing, may in fact indicate future phenoconversion to MSA, whereas normal CAFT results at initial assessment may direct to genetic testing, especially if a SAOA diagnosis was based on a negative family history [74,76]. Cardiovascular autonomic failure can therefore be considered the most specific sign guiding the differential diagnosis of ILOCAs towards MSA [76]. However, because its sensitivity increases with the disease duration, the absence of overt cardiovascular autonomic failure at early stages does not exclude a phenoconversion to MSA later on [74][75][76].…”

“…Cardiovascular autonomic failure can therefore be considered the most specific sign guiding the differential diagnosis of ILOCAs towards MSA [76]. However, because its sensitivity increases with the disease duration, the absence of overt cardiovascular autonomic failure at early stages does not exclude a phenoconversion to MSA later on [74][75][76].…”

Female sexual dysfunction in multiple system atrophy: a prospective cohort study

“…Over the past decade, cumulative evidence has highlighted autonomic failure as a relevant diagnostic and prognostic marker in synucleinopathies. In particular, erectile dysfunction may be an early sign, affecting nearly all men with MSA [2][3][4]9]. The presence of isolated erectile dysfunction enables a diagnosis of possible MSA and is even required, in addition to urinary incontinence, to diagnose probable MSA in male patients.…”