This is an important article as it evaluates the clinical records of 29 patients with autopsy-confirmed multiple system atrophy (MSA) at Mayo Rochester. All 29 of these patients had received “full autonomic function tests.”
CONCLUSIONS
The authors conclude that several factors are “highly predictive” of autopsy-confirmed MSA:
1- “presence of severe generalised autonomic failure”
2- severe adrenergic failure. I believe this is found by testing the blood pressure and heart rate response to the Valsalva manoeuvre and headup tilt.
3- severe sudomotor failure and widespread anhidrosis in particular. Sudomotor failure is determined by the QSART (Quantitative Sudomotor Axon Reflex Test) and the TST (Thermoregulatory Sweat Test).
4- “rapid progression of autonomic failure”
FOUR PHENOTYPES
Among these 29 patients, there were four phenotypes or clinical presentations for MSA:
* MSA-P: 18 of 29
* MSA-C: 8 of 29
* PAF (Pure Autonomic Failure): 2 of 29
* Parkinson’s Disease-like: 1 of 29
Disease duration was shortest for those with the MSA-P phenotype (5 years ± 1.8 years), and longest for those with the PAF phenotype (13 years ± 4.2 years). In between were those with the MSA-C phenotype (8 years ± 3.6 years).
We are told that one of the MSA-P cases was an “atypical” case in which a diagnosis of corticobasal degeneration (CBD) — one of the other atypical parkinsonism disorders — was considered. Due to the “severe generalised autonomic failure,” a diagnosis of MSA-P was made.
In another “atypical” case, PSP was considered due to the patient’s “flexed posture, axial as well as appendicular rigidity, limitation of vertical gaze and hypokinetic dysarthria.” But “given the clinical features of nocturnal stridor and severe generalised autonomic failure, the most likely diagnosis was considered to be MSA.” (This patient was put in the MSA-P group.)
Along with lots of other excerpts, I’ve copied the stories of all of the atypical cases. The few of you who fall into that MSA-vs-PSP-vs-CBD category will want to read those stories. You can really appreciate the challenge for the neurologist in making the clinical diagnosis.
CLINICAL FINDINGS
Some patients had brain MRIs completed. “Cerebellar atrophy was the most common finding (10/16 patients) and the hot cross bun sign was present in two patients.”
The authors provided these two “clinical red flags” — rapid progression and early postural instability:
* “Rapid progression was characteristic, with gait impairment being present at motor onset in 75% of cases; 93% of patients progressed from motor onset to wheelchair dependency within 5 years.”
* “Another characteristic was early postural instability with mean time to first fall of 21±17 months. Retropulsion on the Pull Test was positive in 92% of patients when it was done at 21±18 months from onset of symptoms.”
Here’s what the authors said about parkinsonian symptoms:
* “A rest tremor was uncommon, being present in 10% of patients.”
* “Levodopa responsiveness was poor or poorly sustained in 80%.”
* “Symmetric motor involvement was the rule; symmetric bradykinesia in 78% and rigidity in 80%.”
I hope this is the first of many papers we see out of Mayo on clinical-pathological correlations in MSA.
The abstract is copied below.
Robin
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Journal of Neurology, Neurosurgery, and Psychiatry. 2012 Jan 6. [Epub ahead of print]
Autopsy confirmed multiple system atrophy cases: Mayo experience and role of autonomic function tests.
Iodice V, Lipp A, Ahlskog JE, Sandroni P, Fealey RD, Parisi JE, Matsumoto JY, Benarroch EE, Kimpinski K, Singer W, Gehrking TL, Gehrking JA, Sletten DM, Schmeichel AM, Bower JH, Gilman S, Figueroa J, Low PA.
Neurovascular and Autonomic Medicine Unit, Imperial College London, UK.
Abstract
Background
Multiple system atrophy (MSA) is a sporadic progressive neurodegenerative disorder characterised by autonomic failure, manifested as orthostatic hypotension or urogenital dysfunction, with combinations of parkinsonism that is poorly responsive to levodopa, cerebellar ataxia and corticospinal dysfunction.
Published autopsy confirmed cases have provided reasonable neurological characterisation but have lacked adequate autonomic function testing.
Objectives
To retrospectively evaluate if the autonomic characterisation of MSA is accurate in autopsy confirmed MSA and if consensus criteria are validated by autopsy confirmation.
Methods
29 autopsy confirmed cases of MSA evaluated at the Mayo Clinic who had undergone formalised autonomic testing, including adrenergic, sudomotor and cardiovagal functions and Thermoregulatory Sweat Test (TST), from which the Composite Autonomic Severity Score (CASS) was derived, were included in the study.
Results
Patient characteristics: 17 men, 12 women; age of onset 57±8.1 years; disease duration to death 6.5±3.3 years; first symptom autonomic in 18, parkinsonism in seven and cerebellar in two.
Clinical phenotype at first visit was MSA-P (predominant parkinsonism) in 18, MSA-C (predominant cerebellar involvement) in eight, pure autonomic failure in two and Parkinson’s disease in one.
Clinical diagnosis at last visit was MSA for 28 cases.
Autonomic failure was severe: CASS was 7.2±2.3 (maximum 10).
TST% was 65.6±33.9% and exceeded 30% in 82% of patients. The most common pattern was global anhidrosis.
Norepinephrine was normal supine (203.6±112.7) but orthostatic increment of 33.5±23.2% was reduced.
Four clinical features (rapid progression, early postural instability, poor levodopa responsiveness and symmetric involvement) were common.
Conclusion
The pattern of severe and progressive generalised autonomic failure with severe adrenergic and sudomotor failure combined with the clinical phenotype is highly predictive of MSA.
PubMed ID#: 22228725 (see pubmed.gov for this abstract only)