Progressive supranuclear palsy is not associated with neurogenic orthostatic hypotension

Abstract

ObjectiveTo evaluate the pattern and severity of autonomic dysfunction in autopsy-confirmed progressive supranuclear palsy (PSP) compared to α-synuclein pathology.MethodsAutopsy-confirmed cases of 14 patients with PSP, 18 with multiple system atrophy (MSA), and 24 with Lewy body disease (LBD) with antemortem autonomic testing were reviewed retrospectively. All patients underwent comprehensive clinical evaluations by a movement disorder specialist, formal autonomic testing, and postmortem examinations at Mayo Clinic.ResultsThe absence of orthostatic hypotension (OH) was the strongest autonomic parameter that distinguished PSP from α-synucleinopathies (0% vs 69%, p < 0.0001). Tests of adrenergic failure, which distinguish neurogenic OH, also differentiated PSP from other groups. These included the pressure recovery time (p = 0.0008), adrenergic impairment score (p = 0.001), and magnitude of change of systolic (p = 0.0002) and diastolic (p = 0.0001) blood pressures (BPs) during upright tilt. In addition, REM sleep behavior disorder was seen less frequently (p = 0.006) in PSP (33%) compared to MSA (87%) and LBD (90%). Antemortem clinical diagnostic accuracy for these phenotypically variable disorders was 57% for PSP and 83% for α-synucleinopathies.ConclusionOur results suggest that the cardiovascular adrenergic system, which sustains BP during standing, is relatively unaffected, if not spared, in PSP. These findings increase our understanding of the clinical signature of PSP and have the potential to improve diagnostic accuracy in atypical parkinsonisms by distinguishing PSP from the α-synucleinopathies.

Cutaneous sensory and autonomic denervation in progressive supranuclear palsy

“…This was in line with the lower amplitude of SSR and the more severe loss of autonomic sudomotor nerves associated with frequent aspects of sweat gland derangement. Our findings agree with previous works reporting low amplitudes of sympathetic sweat responses [14] and reduced sweat output by means of the Quantitative Sudomotor Axon Reflex Test (QSART) in PSP [20,24], providing functional and morphological evidence of the postganglionic damage. The loss of autonomic nerves around other dermal adnexa (errector pili muscles, arteriovenous anastomosis, arterioles) was also more severe in PSP compared to PD.…”

“…domain was the most involved in PD patients. This finding is in line with previous studies reporting urinary dysfunction as one of the most common autonomic disturbance in PSP patients [13,24], and the one associated with a more rapid disease progression, together with constipation [25]. Importantly, post-mortem examination showed pathological changes characterised by severe cell loss, presence of neurofibrillary tangles, and glial inclusions of Onuf's nucleus, which is involved in sphincter control [18].…”

“…The PSP Study Group recently stipulated that "predominant, otherwise unexplained autonomic failure" is an exclusionary criterion for PSP [2]. In fact, adrenergic cardiovascular function seems to be spared in PSP as demonstrated by a recent retrospective study on pathologically confirmed PSP, Lewy Body Disease and MSA patients [24]. However, in the same study the authors showed that other autonomic domains, such as sexual, gastrointestinal, sudomotor and urinary, were impaired without any significant difference between PSP and MSA patients [24].…”

Sudomotor Dysfunction

“…35 In contrast, lesser degrees of sudomotor failure have been reported in neurodegenerative disorders unrelated to α-synuclein accumulation, such as progressive supranuclear palsy and sporadic cerebellar degeneration. 32,36 Sudomotor dysfunction occurs in advanced cases of multiple sclerosis. 37,38 As increased core temperature is known to cause transient worsening of neurologic deficits in multiple sclerosis, 39 ineffective thermoregulation from extensive anhidrosis can potentially place patients at risk.…”

‘Falling off’ the dopamine wagon

“…Hallmark symptoms of bradykinesia, rigidity, and postural instability may apply to all forms of parkinsonism. Neurogenic orthostatic hypotension is a manifestation of autonomic dysfunction that may lead to falls and is more common with parkinsonism due to synuclein pathology, such as PD or multiple system atrophy [1,2]. Some persons with parkinsonism may have extraocular eye movement abnormalities, further increasing their risk of falling.…”