and GH levels in MSA (Fig. 2.31). This favors a specific abnormality in the α2-adrenoceptor projection to the hypothalamus in MSA, and indicates that the impaired GH response to clonidine is not due to hypothalamic neuronal cell loss or pituitary malfunction. These neuroendocrine mapping approaches therefore help to determine both the central sites and the neurotransmitters involved, especially in autonomic disorders that may selectively affect one or more neuronal systems and pathways.
Table 2.7 Factors influencing orthostatic hypotension
| Speed of positional change |
| Time of day (worse in the morning) |
| Prolonged recumbency |
| Warm environment (hot weather, central heating, hot bath) |
| Raising intrathoracic pressure: micturition, defecation, or coughing |
| Food and alcohol ingestion |
| Physical exertion |
| Physical maneuvers and positions (bending forward, abdominal compression, leg crossing, squatting, activating calf muscle pump)a |
| Drugs with vasoactive properties (including dopaminergic agents) |
Adapted from [49]
a These maneuvers usually reduce the postural fall in blood pressure, unlike the others.
Fig. 2.26 Twenty-four-hour noninvasive ambulatory blood pressure and heart rate profiles showing systolic (•—•) and diastolic (•···•) blood pressure and heart rate at intervals through the day and night, a Changes in a normal subject with no postural fall in blood pressure; there was a fall in blood pressure at night whilst asleep (an expected circadian nocturnal fail), with a rise in blood pressure on wakening, b Marked fluctuations in blood pressure in a patient with autonomic failure. The falls in blood pressure are usually the result of postural changes, either sitting or standing. Blood pressure when supine, particularly at night, is elevated. Getting up to micturate causes a marked fall in blood pressure (0300 hours). There is a reversal of the diurnal changes in blood pressure. The changes in heart rate are relatively small, considering the large changes in blood pressure. (From [49], with permission)
Fig. 2.27 a The sympathetic skin response (in microvolts) from the right hand and right foot of a normal subject (control) and a patient with dopamine (β-hydroxylase (DBH) deficiency. In pure autonomic failure and pure cholinergic dysautonomia (b) the sympathetic skin response could not be recorded. (From [51], with permission)
In clinical practice, evaluation of autonomic function and dysfunction often needs to be combined with other investigations to determine the causative or associated disease (as in secondary autonomic disorders), and whether there are coexistent diseases or complications. This is of particular importance in diabetes mellitus, where multiple systems may be affected.
Thus investigation of both large and small cerebral vessels (to exclude cerebrovascular disease), neurophysiological assessment (to determine the presence and extent of motor and sensory neuropathy), and allied investigations into urinary bladder, gut, and sexual function may be needed to distinguish between neurogenic failure of target organs and other causes of organ dysfunction (see [44,46,52,53]).
Fig. 2.28 Right anterior cingulate activity showing positive covariance with mean arterial blood pressure (MAP) during isometric exercise and mental arithmetic tasks. Activity in the right anterior cingulate (ac) covaried significantly with increasing blood pressure. For all subjects, regional activity covarying with MAP was computed for isometric exercise and mental arithmetic tasks. (From [54], with permission)
Fig. 2.29 Views of the brain showing activation of the left amygdala using PET scanning with H2150 superimposed on structural magnetic resonance images, and the construction of a statistical parametric map. This was in response to visual stimuli using photographs showing happy and fearful facial expressions. Regional cerebral blood flow (rCBF) is indicated on the right. Faces with fearful expressions caused greater change in blood flow to the amygdala than happy faces. (From [55], with permission)
Fig. 2.30 The upper panel (a) shows mean (SE) serum growth hormone (GH) concentrations before (0) and at 15-minute intervals for 60 minutes after administration of clonidine (2 µg/kg per minute) in normal subjects (controls) and in patients with pure autonomic failure (PAF) and multiple system atrophy (MSA). GH concentrations rise in controls and in patients with PAF with a peripheral lesion; there is no rise in patients with MSA with a central lesion. The lower panel (b) Indicates lack of serum GH response to clonidine In the two forms of MSA (the cerebellar form, MSA-C, and the parkinsonian form, MSA-P), in contrast to patients with idiopathic Parkinson's disease (IPD) with no autonomic deficit, in whom there is a significant rise in GH levels. (From [56], with permission)
Fig. 2.31 Mean (SE) serum growth hormone (GH), plasma human growth hormone releasing hormone (GHRH), and dopamine concentrations before and after administration of l-dopa in nine patients with MSA-P. *P< 0.05 and †P< 0.01 vs basal (time 0). (From [56], with permission)
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