Autopsy confirmed multiple system atrophy cases: Mayo experience and role of autonomic function tests.

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. 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.

Prevalence of orthostatic hypotension in a series of elderly Mexican institutionalized patients.

BACKGROUND: Orthostatic hypotension (OH) is a common problem among the elderly. It is associated with an increase in morbidity and mortality, but its prevalence in Mexico is unknown. METHODS: We conducted a cross-sectional prospective study of intern patients at several Mexican elderly assistance institutions. We carried out a history and took blood pressure readings in a seated position, immediately after standing up, and again after 3 min of standing up. RESULTS: We evaluated 132 patients, mean age 82.3 ± 9.5 years, 74.1% of them female. Thirty-nine (29.3%) subjects had OH. They had a higher prevalence of hypothyroidism, Parkinson's disease, depression and alcoholism. Their Minimental result was 15.45 ± 7.2 vs 16.12 ± 7.9 (p = 0.6) among those without OH, and their quality of life (Minnesota scale) was 12.1 ± 7.3 vs 9.15 ± 7.05 (p = 0.03). They used more ACEI, digoxin and levothyroxin. Hypertension and alcoholism showed respectively a RR of 2.6 (95% CI 0.9-7.6, p = 0.06) and 3.18 (95% CI 0.96-10.48, p = 0.05) to develop OH. CONCLUSIONS: OH was present in 29.3% of the studied population. A third of them had hypertension. The use of different medications does not solely explain OH, so it is necessary to look for different associations. Among those, chronic alcoholism stands out. OH is associated with a poorer quality of life and cognitive performance. OH is asymptomatic in most cases.

Normal cardiovascular reflex testing in patients with parkin disease.

The objective of this study was to investigate cardiovascular autonomic function in patients with parkin disease. Ten patients with a genetically confirmed diagnosis were compared to 11 healthy controls. Symptoms related to autonomic dysfunction were collected by structured interviews. Cardiovascular autonomic reflex function was evaluated using a standard battery of eight tests. Autonomic tests included the study of sympathetic function through the analysis of blood pressure responses to head-up tilt, standing, isometric hand grip, cold pressor, mental arithmetic, Valsalva maneuver (Valsalva overshoot), and the study of parasympathetic function through the analysis of heart rate responses to deep breathing, hyperventilation, and Valsalva ratio. Seven out of 10 patients reported symptoms involving different aspects of autonomic function, while 5 out of 11 controls reported symptoms related exclusively to orthostatic dizziness and constipation. Symptoms related to bladder dysfunction were the most frequent autonomic abnormality occurring in six patients, followed by orthostatic dizziness and dry mouth (in four patients each). Constipation occurred in three patients, sialorrhea in two, and erectile dysfunction, dry eye, and warm intolerance in one each. Cardiovascular reflex testing revealed no difference between patients and controls in quantitative assessment of both sympathetic and parasympathetic functions, except for diastolic blood pressure after isometric hand grip that did not increase normally in parkin patients compared to controls (P = 0.007). These data show that cardiovascular dysautonomia is not associated to the parkin phenotype, whereas urinary complaints are more frequently reported by parkin patients than by controls. Urinary dysautonomia warrants further investigation in patients with parkin disease.

Orthostatic hypotension and attention in Parkinson's disease with and without dementia.

To compare frequency and degree of orthostatic hypotension (OH) in Parkinson's disease (PD) and Parkinson's disease with dementia (PDD) and its effect on attention and word fluency, blood pressure (BP) and heart rate changes during tilt were determined in 10 PD and 8 PDD patients. Attention and word fluency were evaluated in supine and tilted position using standard neuropsychological tests. OH defined as systolic BP (SBP) drop of >/=20 mmHg and/or diastolic BP (DBP) drop of >/=10 mmHg was present in 5 PDD patients and in 2 PD patients. SBP drop was significantly greater in PDD than in PD patients (P < 0.05). Whereas word fluency was unaffected by tilt in both patient groups, attention as assessed with the Test of Everyday Attention (TEA) deteriorated significantly in the PDD group, correlating with blood pressure response (DeltaSBP and TEA-2, r = 0.828, P < 0.05; DeltaDBP and TEA-2, r = 0.828, P < 0.05). We conclude that OH is frequent in PDD and should be addressed therapeutically since it may exacerbate attentional dysfunction.

Dysautonomia and cognitive dysfunction in Parkinson's disease.

Nonmotor symptoms have recently become a focus of renewed clinical interest and research in Parkinson's disease (PD). Autonomic and cognitive dysfunction are among the most prevalent of these nonmotor aspects of the disease. Although exact clinico-pathological correlations have not been established, alpha-synuclein pathology with Lewy body formation in the central and peripheral autonomic nervous system as well as in neocortical areas are generally believed to be driving factors for autonomic failure and cognitive decline in PD. Recent pathological and clinical studies have suggested greater prevalence of clinical dysautonomia and cardiac sympathetic denervation in PD dementia and dementia with Lewy bodies as compared with PD without dementia. This raises the possibility that spread of synuclein pathology to involve neocortical areas producing cognitive decline could be somehow linked to involvement of the autonomic nervous system in PD.

Síndrome de shy-draguer

Se presenta el estudio clínico, farmacológico y electrofisiológico de un varón de 59 años con hipotensión ortostática severa de año y medio de evolución, acompañada por síntomas del sistema nervioso tanto central como periférico: impotencia, anhidrosis "en parches", deficit sensitivo superficial y profundo, temblor de tipo cerebeloso y preservación de las funciones mentales. La sintomatología se acentuó en forma progresiva e incapacitante durante los años de observación. Esta condición corresponde al Síndrome de Shy-Draguer o atrofia multisitémica del sistema nervioso, una entidad de rara ocurrencia caracterizada por degeneración neuronal en los ganglios autónomos, núcleos del tallo cerebral, células de Purkinje, núcleos grises basales y por lesiones cordonales espinales de causa desconocida. El diagnóstico diferencial del Síndrome de Shy-Draguer con otras formas de hipotensión ortostática (mal ajuste postural y formas secundarias), que ocurren con mayor frecuencia, es de importancia terapéutica y pronostica