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A 33-year-old woman with acute idiopathic post-ganglionic panautonomic neuropathy experienced prompt recovery of all dysautonomic symptoms after receiving high-dose intravenous immunoglobulin therapy. Her recovery was complete within 6 months after onset of disease. This unusually rapid and complete recovery in comparison with that of historical control subjects suggests that patients with acute, severe, and widespread autonomie failure might benefit from intravenous immunoglobulin therapy.
Panautonomic neuropathy (pandysautonomia) is part of the group of neuropathies characterized by parasympathetic and sympathetic failure with minimal or no somatosensory or motor impairment.
The syndrome is thought to result from an immune-mediated mechanism that can complicate specific disorders (for example, malignant lesions and connective tissue diseases), but the postviral and idiopathic variants are the most common.
The site of autonomie failure is usually in the efferent postganglionic pathways. Slow, incomplete recovery and persistent orthostatic hypotension are common, and as yet no effective therapy is available.
In the Guillain-Barré syndrome, the immune-mediated somatic counterpart of acute panautonomic neuropathy (APN), intravenous immunoglobulin (IVIg) therapy has been shown to have beneficial effects.
Herein we describe a severely ill patient with APN who recovered after receiving IVIg therapy.
Report of Case
A 33-year-old woman had left-sided ptosis, dry mouth, abdominal cramps, and constipation after 6 days of malaise with no fever. After 17 days, she experienced postural dizziness and blurred near vision of the right eye; in addition, she had to compress her lower abdominal area in order to urinate. On the 25th day of illness, she was admitted to our medical center.
On admission of the patient, supine mercury sphygmo-manometric blood pressure was 110/70 mm Hg. Her heart rate did not change on deep breathing. When she was upright, her blood pressure decreased to 60/30 mm Hg, and she could stand less than 30 seconds. Skin and mucous membranes were dry, and sweating was noted only on the forehead. Both pupils were neither miotic nor dilated but were of a mid-dilatory size, and they were nonreactive. Accommodative power in both eyes was reduced (right, 4 diopter [D]; left, 6 D; normal, greater than 7). The left eye was ptotic, but ptosis disappeared on upward gaze. No sensory or motor disturbances were found.
Results of routine blood chemistry and hématologie studies were normal. Antinuclear antibodies and sérologie tests for neurotrophic viruses, Borrelia, and syphilis were negative. A cerebrospinal fluid examination and computed tomo-graphic scan of the brain revealed no abnormalities. Findings on electroneurographic motor and sensory conduction studies, late response studies, and computer-assisted heat and cold threshold detection (Triple T, Vickers, Nieuwkoop, The Netherlands) were normal.
After unexpected noise, forced breathing, and electrical stimulation, sympathetic skin potential responses were reduced in the right hand (0.09 mV; normal, greater than 0.5) and absent in the feet.
When the patient was standing and during Valsalva straining, the finger arterial pressure (Finapres, TNO-BioMedical Instrumentation, Amsterdam, The Netherlands) decreased progressively with no increase in heart rate, an indication of impaired vasoconstriction and absent cardio-parasympathetic and cardiosympathetic responses (Fig. 1).
in: Bannister R Mathias CJ Autonomie Failure: A Textbook of Clinical Disorders of the Autonomie Nervous System. 3rd ed. Oxford University Press,
Oxford (England)1992: 255-290
Non-invasive continuous recording of heart rate and blood pressure in the evaluation of neurocardiovascular control.
in: Bannister R Mathias CJ Autonomie Failure: A Textbook of Clinical Disorders of the Autonomie Nervous System. 3rd ed. Oxford University Press,
Oxford (England)1992: 291-311
During orthostatic hypotensive stress, in which the finger blood pressure decreased from 117/67 mm Hg to 80/47 mm Hg, the baroreceptor-mediated vasopressin release increased adequately from 0.3 ng/L (normal, 0.2 to 1.5) to 3.4 ng/L, an outcome that established integrity of afferent baroreceptor pathways. During the cold pressor test, an abnormally small pressor response was found (systolic/diastolic, 7/5 mm Hg; normal, 10 to 20/10 to 15). While the patient was supine, forearm plasma noradrenaline was extremely low (0.09 nmol/L; normal, 0.86 to 3.40), and adrenaline was normal (0.05 nmol/L; normal, 0.05 to 0.82). During orthostatic hypotensive stress, no increases occurred in adrenaline, and noradrenaline decreased by 0.02 nmol/L. Analysis of these results established that the site of vasomotor failure was in the efferent pathways.
in: Bannister R Mathias CJ Autonomie Failure: A Textbook of Clinical Disorders of the Autonomie Nervous System. 3rd ed. Oxford University Press,
Oxford (England)1992: 255-290
Fig. 1Finger arterial blood pressure and heart rate responses in patient with acute panautonomic neuropathy. Note severe, progressive decrease in blood pressure with no change in heart rate when patient was standing (upper left) and during Valsalva straining at 30 mm Hg when she was supine (lower left). Right-hand panels were obtained 5 months after intravenous immunoglobulin treatment. Valsalva ratio increased from 1.0 to 1.6.
Low-dose bolus injections of intravenous phenylephrine, 12.5 g and 25 g, produced enhanced pressor responses (35/30 mm Hg and 37/25 mm Hg), an indication of denervation supersensitivity. Normally, no pressor response is noted with such doses.
The pronounced increases in blood pressure induced almost no change in heart rate (from 70 to 68 and from 71 to 69 beats/min, respectively). Intradermal acetylcholine (10 mg) elicited no sweat response orpiloerection. On the basis of these observations, we located the site of vasomotor and sudomotor failure in the postganglionic sympathetic pathways.
Management with expansion of total body water (daily dietary intake of 200 mmol of sodium chloride, sleeping in a head-up tilt position, and 0.1 mg of fludrocortisone acetate) and performance of physical countermaneuvers
improved orthostatic intolerance, but postural hypotension and the other dysautonomic symptoms remained. Thirty days after the onset of symptoms, a total of 140 g of IVIg therapy (Sandoglobulin, Sandoz Pharma, Switzerland; 1 g/kg of body weight per day for 2 consecutive days) was administered. Five days after the infusion of IVIg, the right pupil reacted slightly to light. Production of saliva and hesitancy of micturition had improved, and constipation had resolved. Syncope or disabling dizziness no longer occurred, but orthostatic hypotension was still severe, and instantaneous heart rate changes were almost absent (supine—blood pressure 132/88 mm Hg and heart rate 68 beats/min; after standing for 1 minute—93/60 mm Hg and 74 beats/min, respectively). During outpatient follow-up, dysautonomic symptoms diminished further. Two months after administration of IVIg therapy, orthostatic hypotension was no longer present (supine, 129/74 mm Hg; after standing for 1 minute, 124/78 mm Hg; and after 5 minutes, 122/78 mm Hg).
The patient had complete symptomatic recovery within 6 months after onset of disease. Findings on neurologic and electroneurophysiologic examinations were normal except for a reduction in heat discrimination at the ankles (right, 3.4C; left, greater than 10C; normal, less than 2.1C). The sympathetic skin potential responses had returned to normal. On standing and during the Valsalva maneuver, blood pressure and heart rate responses were normal (Fig. 1). The heart rate response to forced breathing of 20/min was normal. While the patient was supine, forearm plasma noradrenaline was slightly reduced (0.78 nmol/L; normal, 0.86 to 3.40), but a normal increase (1.37 nmol/L; normal, 0.71 to 4.14) was found after she had stood 5 minutes. At 1-year follow-up, she was still asymptomatic.
Discussion
Our patient had postganglionic idiopathic APN; associated prognosis is poor.
of these, only two patients recovered completely from ortho-static hypotension and other dysautonomic impairments at follow-up of 21 months and 3 years, respectively.
Similarly, in a retrospective study of 27 patients with preganglionic or postganglionic subacute idiopathic autonomie neuropathy, laboratory investigations showed that, a mean of 2 years after the symptoms had begun, severe autonomie failure was present in 63%, ortho-static hypotension in 63%, and reduced heart rate variability in 63%. During a subsequent follow-up of 32 months, the prognosis to recovery remained poor in the entire group.
Although a spontaneous improvement cannot be excluded in our patient, the complete and rapid recovery after IVIg therapy suggests a beneficial effect from IVIg. A recent publication reported a case of APN in which high-dose IVIg therapy was administered during the early stage of disease.
Substantial improvement in most autonomie disturbances supported the beneficial effects of IVIg. Because of the poor prognosis of this severely disabling disorder, the absence of effective therapy thus far, and its similarity with the Guillain-Barré syndrome in which IVIg is a recognized therapy, IVIg should be considered in the treatment of patients examined within 1 month after onset of severe, widespread autonomie failure.
References
Yokota T
Hayashi M
Hirashima F
Mitani M
Tanabe H
Tsukagoshi H
Dysautonomia with acute sensory motor neuropathy: a new classification of acute autonomie neuropathy.
in: Bannister R Mathias CJ Autonomie Failure: A Textbook of Clinical Disorders of the Autonomie Nervous System. 3rd ed. Oxford University Press,
Oxford (England)1992: 255-290
Non-invasive continuous recording of heart rate and blood pressure in the evaluation of neurocardiovascular control.
in: Bannister R Mathias CJ Autonomie Failure: A Textbook of Clinical Disorders of the Autonomie Nervous System. 3rd ed. Oxford University Press,
Oxford (England)1992: 291-311