Secondary Logo

Journal Logo

Pupil Abnormalities in Selected Autonomic Neuropathies

Bremner, Fion D PhD; Smith, Stephen E PhD

Journal of Neuro-Ophthalmology: September 2006 - Volume 26 - Issue 3 - p 209-219
doi: 10.1097/01.wno.0000235564.50518.1b
State of the Art

Examination of the pupil provides an opportunity to detect disturbances in the autonomic innervation of the eye. The pupil is frequently affected in patients with generalized autonomic neuropathies. This literature review confirms a high prevalence of sympathetic deficits and parasympathetic deficits in acute or subacute dysautonomia, diabetes, amyloidosis, pure autonomic failure, paraneoplastic syndromes, Sjögren syndrome, familial dysautonomia, and dopamine β-hydroxylase deficiency. It confirms the relative scarcity of a pupil abnormality in patients with multiple system atrophy. There are difficulties in clinical diagnosis of pupil abnormalities and interpretation of pupil pharmacologic tests, particularly when combined sympathetic and parasympathetic deficits are present.

Department of Neuro-ophthalmology, National Hospital for Neurology and Neurosurgery, London, United Kingdom.

Address correspondence to Stephen E. Smith, PhD, Department of Neuro-ophthalmology (Box 142), National Hospital for Neurology & Neurosurgery, Queen Square, London WC1N 3BG, United Kingdom; E-mail:

Autonomic neuropathy is characterized by cardiovascular, gastrointestinal, genitourinary, and sweat gland dysfunction. In most cases, sympathetic and parasympathetic branches of the autonomic nervous system are involved, although in a few instances, there is selective hypofunction in one or another branch. Pupil abnormalities have been widely reported in association with generalized autonomic failure but, except in diabetes, rarely investigated in detail.

In this review, we have used electronic (Medline, PubMed) and manual techniques to search the literature for published reports of pupil abnormalities in selected autonomic neuropathies. Most reports are anecdotal-based on clinical observations and only sometimes supported by confirmatory tests. With the exception of diabetes mellitus, there are no systematic studies of pupil involvement in these conditions. The findings have been grouped according to etiology, and we have assessed the evidence for the pupil signs before attempting to draw sweeping conclusions.

Because the pupil constrictor muscle is supplied by parasympathetic fibers and the dilator by sympathetic fibers, complete failure of iris innervation should result in a pupil of medium diameter that is unresponsive to light, near, and alarm stimuli, although persistence of adrenal medullary function might allow slow dilator responses to stress from circulating catecholamines. Very few such instances of “pupilloplegia” are reported except in cases of acute or subacute pandysautonomia.

Selective parasympathetic denervation should result in relative mydriasis in light and diminution in constrictor reflexes with or without pupillotonia (which is thought to result from aberrant reinnervation [1]). Selective sympathetic denervation should result in relative miosis in darkness with dilatation lag (2) and diminution of the startle reflex as seen in Horner syndrome (3,4). In all such instances, the pupil would be expected to show supersensitivity to topical administration of receptor agonists (2% or 2.5% methacholine and 0.1% or 0.125% pilocarpine at the sphincter muscle, 1% phenylephrine or 1% epinephrine at the dilator muscle).

Back to Top | Article Outline


This acute or subacute condition is characterized by widespread dysfunction of one, or more usually both, branches of the autonomic nervous system coupled occasionally with somatic sensory or sensorimotor impairment. In some cases, it follows an episode of influenza-like illness and recovery is variable.

Acute and subacute dysautonomia commonly involve the pupil. Published cases (Table 1) can be divided into several forms: a predominantly cholinergic type affecting the parasympathetic nervous system (5-19), an adrenergic type affecting the sympathetic nervous system (20,21), a mixed type (22-51,202), and forms with additional involvement of sensory (52-63) or sensorimotor peripheral nerves (64).



Despite differences in clinical presentations, the pupil findings in cases within the different groups are essentially similar. The shape of the pupil is often oval or irregular in outline. Mydriatic pupils are described as having a poor reaction to a light stimulus or a target viewed at reading distance (“near target”). The only exception is one reported case of the acute adrenergic type whose pupils were small and who appeared to have bilateral Horner syndrome (20). The majority of patients have not undergone formal pharmacologic testing, but among patients who were tested, 75% showed evidence of sympathetic deficit (7,14,17,19,24-27,31,32,34,36,42,43,46,49,50,53,58-60) and 90% demonstrated parasympathetic deficit (7,8,10-12,14,17-19,22,25-28,31-37,40,42,43,46,53,58-60). Overall, the findings indicate that a high proportion of these cases involve both parasympathetic and sympathetic denervation of the pupil.

Recent observations suggest that these pupil abnormalities may result from widespread autonomic ganglionopathy and they are strongly linked to the presence of autoantibodies to ganglionic cholinergic receptors (65-67). Acute dysautonomia in cats and dogs also causes mydriasis, reduced or absent light reflexes, and supersensitivity to both pilocarpine and epinephrine (68-70).

Back to Top | Article Outline


The pupil is frequently abnormal in both types of diabetes mellitus: type 1 or insulin-dependent diabetes, which is commonly of early onset; and type 2 or noninsulin-dependent diabetes, which is usually of later onset.

The most common observation is that the pupil is miotic (71-77), particularly in darkness. A screening study of 359 unselected diabetic patients found that 21.7% had abnormally small pupils for age (78). Significant associations between small pupils and a wide range of diabetic complications have been recorded: cardiovascular autonomic dysfunction (79), peripheral sensory loss (73,77), retinopathy (80), nephropathy (73), and unduly prolonged and severe hyperglycemia (73,77). Acute hyperglycemia may cause miosis that reverses when normoglycemia is established (81,82).

The common occurrence of a small pupil with intact light reflexes, in contrast to the rarity of a large pupil with poor light reflexes, suggests that the sympathetic iris innervation is more susceptible to damage than the parasympathetic innervation. Histologic studies of irides removed from patients with diabetes during cataract surgery have confirmed that loss of nerve terminals occurs preferentially from the dilator pupillae (83,84). The reason for the greater susceptibility of the sympathetic nerves is unknown; it may be related to the greater length of the nerve pathway (90).

The mydriatic response to direct-acting sympathomimetic agents is exaggerated in patients with diabetic autonomic neuropathy (79,80), implying denervation supersensitivity (85,86). In one study (79), severe miosis was found to be associated with supersensitivity to phenylephrine but normal responses to the indirect-acting sympathomimetic hydroxyamphetamine. These findings indicate that diabetic miosis is at least partly neuropathic in origin but that the postganglionic neuron remains functionally intact. It seems unlikely that diabetes blocks transmission of sympathetic impulses at any one point along the sympathetic pathway; more probably the deficit results from a composite of mildly reduced function throughout.

The anticholinergic drug tropicamide produces less mydriasis in diabetic pupils than in nondiabetic pupils, presumably because of the loss of effective pupil dilator function. Some observers have used measurement of the pupil response to a large dose of an anticholinergic to assess dilator muscle function and thus, indirectly, the percent of diabetic neuropathy (75,87). Full mydriasis in practice requires combined instillation of tropicamide and phenylephrine (88).

The amplitude of the pupillary constriction to light is reduced in diabetic pupils (89,90). Light reflexes, if present, are slow in onset and time course, giving prolonged latency times and reduced maximum velocities of constriction and redilatation (77). This reduction is usually found only in pupils that are already small from sympathetic dysfunction. In severely affected patients, therefore, pupil size remains almost constant despite wide changes in illumination. There are a number of possible explanations for this. First, neovascularization of the iris (rubeosis) may have stiffened the iris and immobilized the pupil. Recent evidence also shows that patients with type 2 diabetes can develop iris transillumination defects, particularly if there is severe retinopathy, suggesting hypoxic damage to the iris (91). Second, retinopathy and laser photocoagulation treatment attenuate the afferent limb of the pupil light reflex. Third, it is likely that damage to the parasympathetic supply underlies at least some of the observed reduction in pupil light responses. The pupil will constrict after topical administration of pilocarpine (80), and light reflexes are attenuated even after adjustments are made to the stimulus intensity to take into account differences in retinal sensitivity (90). Presumably, the iris in such patients is essentially denervated in both autonomic branches. The enhanced response of the diabetic pupil to cholinomimetic agents such as pilocarpine (80) supports this hypothesis.

Random variation in the pupil diameter when the eye is exposed to constant illumination, known as hippus, is always symmetric in the two eyes and thought to be central in origin (92). Patients with diabetes with neuropathy show reduced hippus compared with healthy subjects (77,93). It is not clear whether this phenomenon is the result of peripheral damage to the autonomic nerves and iris muscles or whether the central control centers for pupil size are affected.

Back to Top | Article Outline


Systemic amyloidosis consists of a heterogenous group of conditions characterized histologically by deposition of abnormal birefringent protein in tissues. The protein responsible for most cases of familial amyloid (AF) polyneuropathy is transthyretin, whereas the most common form of acquired amyloidosis (AL) involves deposition of light-chain paraproteins.

Clinical features suggestive of widespread damage to the autonomic nervous system are well recognized, although uncommon, in both AF and AL. In their survey of 229 cases of AL seen at the Mayo Clinic, Kyle and Greipp (94) reported 31 (14%) patients who had orthostatic hypotension. Among the subset of patients with AL who develop polyneuropathy, however, autonomic dysfunction appears to be common. Thus, Trotter et al (95) found orthostatic hypotension in 8, bowel upset in 9, and impotence in 8 of 10 patients. There is histopathologic evidence of amyloid deposition in the sympathetic ganglia and sympathetic chain (96-99).

The most apparent ophthalmic manifestation of amyloidosis is amyloid deposition in the lids, extraocular muscles, ocular adnexae (100-104), and the eye, especially the vitreous gel (105-108). Pupillary abnormalities have been reported, usually in association with other evidence of autonomic dysfunction. In 21 reported cases (Table 2), the pupil abnormality was reported as hyporeactive (109), asymmetric or unreactive (95), or showing light-near dissociation (110-112). One case (112) was reported as having bilateral “Holmes-Adie” pupils, parasympathetic denervation being confirmed by finding supersensitivity to methacholine (96). These pupil abnormalities are consistent with a parasympathetic deficit for which amyloid deposition in the ciliary ganglion may be responsible (113,114). Bilateral pupil dilatation lag, which indicates a sympathetic deficit, has also been reported in patients with amyloidosis and autonomic neuropathy. In at least one of these cases, amyloid deposition in the sympathetic chain appeared to be responsible (115).



Back to Top | Article Outline


Multiple system atrophy (MSA; Shy-Drager syndrome) is a progressive condition associated with a variable incidence of extrapyramidal disorder with parkinsonism, cerebellar dysfunction, and dysautonomia. The condition is often accompanied by a sleep disturbance and bladder dysfunction. It is notoriously unresponsive to antiparkinsonian medication.

Pupil abnormalities are occasionally found in MSA (Table 2). In their original description of this condition, Shy and Drager (116) described iris atrophy and anisocoria in both of their patients. One of them had ptosis and miosis in one eye and also had reduced pupillary reactions to light and near. Anisocoria has appeared frequently in subsequent reports (117-123), although some patients with MSA may have had unilateral Horner syndrome (117,118,124) or alternating Horner syndrome as reported in 6 patients (125-127). The mechanism is obscure.

Despite widespread autonomic dysfunction, however, many patients with MSA have been found to have normal pupils. In one series (117), 40 (70%) of 57 patients had normal pupils, and the pupils have been reported as normal in this condition by many others (42,124,126,128-130).

Back to Top | Article Outline


Pure autonomic failure (PAF) is a variably progressive idiopathic condition often occurring in later life in which there is widespread autonomic dysfunction without disturbance of the central nervous system or involvement of the peripheral somatic nerves.

The pupil has been rarely studied in detail in PAF. In their original study, Bradbury and Eggleston (131) observed that the pupils of their two patients were misshapen but that they reacted normally. Although many patients have no pupillary abnormality (24,132-135), absent light reflexes with light-near dissociation have been reported once (136). Bilateral ptosis has been observed (24) and Horner syndrome reported (4,133,135) with adrenergic supersensitivity found in 3 cases. Polinsky et al (133) reported that tyramine, an indirect-acting sympathomimetic agent similar to hydroxyamphetamine, was associated with reduced pupillary dilatation in patients with PAF relative to controls. This difference is consistent with the belief that PAF is a disease of peripheral neurons, whereas MSA is a disease of central neurons.

Back to Top | Article Outline


Immune responses to tumors may cause remote (nonmetastatic) effects on specific target organs, including peripheral nerves, giving rise to various paraneoplastic syndromes.

Pupil abnormalities have been widely reported in patients with a number of paraneoplastic syndromes, including Lambert-Eaton myasthenic syndrome (LEMS) (Table 2). Bilateral tonic pupils, absent or sluggish reactions to light, and prolonged pupil cycle times have been described in 13 LEMS cases (137-143). Unspecified pupil dysfunction has been noted in 4 cases (144), and supersensitivity to cholinergic (139,141,145-148) and adrenergic (141,149) agents in 8 cases. The aggregate frequency of reported pupil abnormalities in LEMS is 24% (21 of 88) (150).

Pupil abnormalities also occur in other paraneoplastic syndromes. Bilateral tonic pupils with pilocarpine supersensitivity have been reported in 3 infants with neuroblastoma (147,148) and in adults with presumed anti-Hu-mediated neuronopathies associated with small cell lung carcinoma (151-154), adenocarcinoma of the colon (155), and testicular seminoma (145). There is one report of bilateral Horner syndrome associated with anti-Hu-mediated demyelinating neuropathy and small cell lung carcinoma (156). Unilateral tonic pupils with or without cholinergic supersensitivity have been reported in 4 cases (157-160), but the pupillotonia may be indicative of coincidental Holmes-Adie syndrome (3 of the 4 cases had tendon areflexia) and are therefore difficult to interpret.

Back to Top | Article Outline


Sjögren syndrome is characterized by keratoconjunctivitis sicca, xerostomia, and numerous extraglandular manifestations that may overlap with rheumatoid arthritis. When these manifestations are part of another connective tissue disorder, Sjögren syndrome is considered secondary.

Autonomic neuropathy is a common complication of primary and secondary Sjögren syndromes. Unilateral or bilateral tonic pupils occur, usually with light-near dissociation (161-172). Similar findings have been reported in patients with sicca syndrome in whom a definitive diagnosis of Sjögren syndrome had not yet been made (173,174). The recent demonstration of autoantibodies against M3-muscarinic acetylcholine receptors in patients with Sjögren syndrome suggests that the pupil abnormality may be caused by receptor blockade rather than sphincter muscle denervation in some cases (175,176).

Back to Top | Article Outline


The familial condition of hereditary sensory and autonomic neuropathy type III (HSAN III), occurring almost exclusively in Ashkenazi Jews, is characterized by widespread sensory and autonomic disturbance. The hallmark ophthalmic signs of HSAN III are alacrima and corneal hypesthesia (177); ulceration and scarring of the corneas are common and blindness may occur.

Pupil abnormalities have been widely reported in HSAN III, largely on the basis of pharmacologic evidence. The most common feature, an exaggerated miotic response to 2.5% topical methacholine or 0.1% or 0.125% pilocarpine, is usually attributed to denervation supersensitivity of the iris sphincter muscle (178-189). Such supersensitivity is no longer regarded as pathognomonic of the condition because it is to be expected in any other condition in which there is parasympathetic denervation (190). Moreover, not all the evidence supports parasympathetic dysfunction. Three early studies (188,191,192) showed that the pupils of these patients react normally to light and a near target, and that there is no pupillotonia or light-near dissociation. The responses to topical anticholinesterases (physostigmine, neostigmine, and echothiophate) have also been unremarkable in some patients with HSAN III (or in a single case, slightly exaggerated [178]). Such findings would suggest that the parasympathetic innervation in HSAN III is intact.

In most patients with HSAN III, the autonomic neuropathy is characterized principally by sympathetic deficits with parasympathetic dysfunction sometimes occurring later. Pupil sympathetic function has rarely been studied in detail. Normal responses to both cocaine and epinephrine were reported in 20 patients (178,181) and an exaggerated response to phenylephrine in only one (180). A recent study comparing pupil measurements in 14 patients with age-matched healthy controls showed a reduction in pupil diameter in darkness and redilatation velocity, as well as attenuation of the light reflex, possibly indicating mixed sympathetic and parasympathetic failure (193). The differences found were surprisingly small but did achieve statistical significance.

Back to Top | Article Outline


In dopamine β-hydroxylase deficiency, a rare inherited condition, subjects lack the enzyme dopamine β-hydroxylase and therefore cannot synthesize norepinephrine from dopamine, causing a pure sympathetic deficit (194-199).

The pupils have been described as small (2-3 mm in diameter) but normally reactive (194,195,197) with supersensitivity to topical epinephrine (198) and phenylephrine (197) but no response to hydroxyamphetamine (196), the indirect action of which requires a functional postganglionic sympathetic neuron. Later pupillographic studies of a sibling pair (198) revealed severe bilateral redilatation lag (4) consistent with these abnormalities. As expected, the pupils showed no supersensitivity to methacholine (194,196,198) and did not dilate with the atropinic agent homatropine (196).

Back to Top | Article Outline


A systematic literature review confirms that patients with widespread autonomic dysfunction are often reported as having abnormal pupils. For several reasons, the detection and characterization of these pupil abnormalities can be challenging. The initial clinical examination is often unremarkable because the pupil abnormalities are commonly bilateral and symmetric. The pupils are rarely misshapen even when tonic; anisocoria may not be present under any lighting conditions; and clinical detection of an abnormal response to light or near has a low sensitivity. Reports of abnormal pupils associated with generalized dysautonomia are therefore likely to underestimate their actual prevalence if based on clinical observations alone.

It should be possible to overcome these difficulties in part by using pharmacologic tests to demonstrate denervation supersensitivity to weak receptor agonists. However, care must be taken in the interpretation of such findings because many patients with autonomic neuropathy have impaired tear formation with or without corneal damage. In such circumstances, transcorneal drug penetration may be enhanced (188), thus giving rise to an apparent but false supersensitivity (200). This is well illustrated by a recent report of a patient with Sjögren syndrome with dry eyes in whom both pupils were supersensitive to norepinephrine but there was no impairment of the sympathetic supply as demonstrated by a normal mydriatic response to cocaine (201). Drug testing may therefore tend to overestimate the prevalence of pupil abnormalities in patients with tear film disturbance. Furthermore, the lack of a “control” eye and the possibility that both parasympathetic and sympathetic supplies are affected make interpretation of pupillary responses to different drugs particularly difficult.

In many patients with dysautonomia, iris sphincter and dilator muscles are both likely to be denervated to some percent, but if one deficit predominates, it will mask the other. For example, a patient with bilateral tonic pupils may also have a sympathetic deficit. However, with isocoria and symmetric lids, and without a “control” eye against which to compare redilatation times or responses to topical cocaine, it is impossible to prove any sympathetic deficit. A patient with bilateral Horner syndrome might also have a mild parasympathetic deficit, but the subtle changes in light diameter and responses to light and a near target would be masked by the changes in resting diameter resulting from the sympathetic deficit. Drug tests may be useful but the results should be interpreted with caution. In practice, pupil abnormalities are most commonly interpreted as indicating either sympathetic or parasympathetic denervation; it is rarely possible to diagnose confidently damage to both arms of the autonomic system in the pupils of an individual patient.

Back to Top | Article Outline


1. Loewenfeld IE, Thompson HS. The tonic pupil: a re-evaluation. Am J Ophthalmol 1967;63:46-87.
2. Lowenstein O, Loewenfeld IE. Mutual role of sympathetic and parasympathetic in shaping of the pupillary reflex to light; pupillographic studies. Arch Neurol Psychiatry 1950;64:341-77.
3. Pilley SJ, Thompson HS. Pupillary ‘dilatation lag’ in Horner's syndrome. Br J Ophthalmol 1975;59:731-5.
4. Smith SA, Smith SE. Bilateral Horner's syndrome: detection and occurrence. J Neurol Neurosurg Psychiatry 1999;66:48-51.
5. Young RR, Asbury AK, Corbett JL, et al. Pure pan-dysautonomia with recovery. Trans Am Neurol Assoc 1969;94:355-7.
6. Young RR, Asbury AK, Corbett JL, et al. Pure pan-dysautonomia with recovery. Brain 1975;98:613-36.
7. Andersen O, Lindberg J, Modigh K, et al. Subacute dysautonomia with incomplete recovery. Acta Neurol Scand 1972;48:510-9.
8. Thomashefsky AF, Horwitz SF, Feingold MH. Acute autonomic neuropathy. Neurology 1972;22:251-5.
9. Harik SI, Ghandour MH, Farah FS, et al. Postganglionic cholinergic dysautonomia. Ann Neurol 1977;1:393-6.
10. Hopkins IJ, Shield LK, Harris M. Subacute cholinergic dysautonomia in childhood. Clin Exp Neurol 1981;17:147-51.
11. Inamdar S, Easton LB, Lester G. Acquired postganglionic cholinergic dysautonomia: case report and review of the literature. Pediatrics 1982;70:976-8.
12. Kirby RS, Fowler CJ, Gosling JA, et al. Bladder dysfunction in distal autonomic neuropathy of acute onset. J Neurol Neurosurg Psychiatry 1985;48:762-7.
13. Takayama H, Kazahaya Y, Kashihara N, et al. A case of postganglionic cholinergic dysautonomia. J Neurol Neurosurg Psychiatry 1987;50:915-8.
14. Hart RG, Kanter MC. Acute autonomic neuropathy. Two cases and a clinical review. Arch Intern Med 1990;150:2373-6.
15. Benini LM, Bardell EA, Bongiovanni LG, et al. Acute dysautonomia may cause transient oesophageal aperistalsis mimicking achalasia. Eur J Gastroenterol Hepatol 1993;5:1067-70.
16. Baron R, Engler F. Postganglionic cholinergic dysautonomia with incomplete recovery: a clinical, neurophysiological and immunological case study. J Neurol 1996;243:18-24.
17. Kim DW, Park KI, Jung KH, et al. A case of incomplete postganglionic cholinergic dysautonomia. J Neurol 2003;250:316-9.
18. Sakakibara R, Uchiyama T, Asahina M, et al. Micturition disturbance in acute idiopathic autonomic neuropathy. J Neurol Neurosurg Psychiatry 2004;75:287-91.
19. Yamamoto K, Kato NA, Oide T, et al. Successful pharmacotherapy for an adult case with prolonged symptoms of postganglionic cholinergic dysautonomia. Eur Neurol 2004;51:244-6.
20. Voorhies TM, Tardo CL, Amodeo C, et al. Neurogenic orthostatic hypotension in an adolescent. Ann Neurol 1984;16:407.
21. Bannister R, da Costa DF, Hendry WG, et al. Atrial demand pacing to protect against vagal overactivity in sympathetic autonomic neuropathy. Brain 1986;109:345-56.
22. Laufer ST. Orthostatic hypotension. Can Med Assoc J 1942;46:160-4.
23. Barnett AJ, Wagner GR. Severe orthostatic hypotension: a case report and description of response to sympatheticomimetic drugs. Am Heart J 1958;56:412-24.
24. Hughes RC, Cartlidge NE, Millac P. Primary neurogenic orthostatic hypotension. J Neurol Neurosurg Psychiatry 1970;33:363-71.
25. Goulon M, Nouailhat F, Grosbuis S, et al. Hypotension orthostatique à pouls invariable. Étude hémodynamique d'une neuropathie amyloide et d'une forme idiopathique transitoire. Rev Neurol (Paris) 1971;125:257-72.
26. Appenzeller O, Kornfeld M. Acute pandysautonomia: clinical and morphological study. Arch Neurol 1973;29:334-9.
27. Hopkins A, Neville B, Bannister R. Autonomic neuropathy of acute onset. Lancet 1974;1:769-71.
28. Okada F, Yamashita I, Suwa N. Two cases of acute pandysautonomia. Arch Neurol 1975;32:146-51.
29. Yahr MD, Frontera AT. Acute autonomic neuropathy. Its occurrence in infectious mononucleosis. Arch Neurol 1975;32:132-3.
30. Yee RD, Trese M, Zee DS, et al. Ocular manifestations of acute pandysautonomia. Am J Ophthalmol 1976;81:740-4.
31. Christie DL, Knauss TA. Gastrointestinal manifestations of ‘acquired dysautonomic’ syndrome. J Pediatr 1979;94:625-8.
32. Guidi L, Zeppilli P, Sassara M, et al. Alterazioni del controllo autonomoptropo cardiovascolare in un caso di pandisautonomia acuta con remissione clinica. G Ital Cardiol 1981;11:1151-9.
33. Bost M, Rossignol AM, Tachker D, et al. Un cas de dysautonomie aigue reversible chez l'adolescent. Pédiatrie 1983;38:29-36.
34. Low PA, Dyck PJ, Lambert EH, et al. Acute panautonomic neuropathy. Ann Neurol 1983;13:412-7.
35. Neville BG, Sladen GE. Acute autonomic neuropathy following primary herpes simplex infection. J Neurol Neurosurg Psychiatry 1984;47:648-50.
36. van Lieshout JJ, Wieling W, Montfrans GA, et al. Acute dysautonomia associated with Hodgkin's disease. J Neurol Neurosurg Psychiatry 1986;49:830-2.
37. Okada F, Shintomi Y, Kase M. Pupillary symptoms in three patients with pandysautonomia. J Neuroophthalmol 1988;8:87-93.
38. Watanabe S, Shimazu K, Hosokawa T, et al. An adult case of acute pandysautonomia with rubella infection. Auton Nerv Syst 1988;25:432-7.
39. Ali A. Acute autonomic neuropathy associated with infectious mononucleosis. Ann Neurol 1990;28:462.
40. Feldman EL, Bromberg MB, Blaivas M, et al. Acute pandysautonomic neuropathy. Neurology 1991;41:746-8.
41. Stoll G, Thomas C, Reiners K, et al. Encephalo-myelo-radiculo-ganglionitis presenting as pandysautonomia. Neurology 1991;41:723-6.
42. Yazawa M, Ikeda S, Ushiyama M, et al. Noradrenergic nerve fibres of the rectal mucosa in autonomic disorders: comparison of histochemical study with clinical severity and changes in plasma noradrenaline induced by standing. J Neurol Sci 1991;104:222-9.
43. Li S, Guo Y. Pandysautonomia: clinicopathological. Report of 5 cases. Chin Med J 1995;108:829-34.
44. Bennett JL, Mahalingam R, Wellish MC, et al. Epstein-Barr virus associated acute autonomic neuropathy. Ann Neurol 1996;40:453-5.
45. Ushiyama M, Ikeda S, Suzuki T, et al. Acute pandysautonomia: mass spectrometric and histopathological studies of the sympathetic nervous system during long term L-threo-3,4-dihydroxyphenylserine treatment. J Neurol Neurosurg Psychiatry 1996;61:99-102.
46. Mericle RA, Triggs WJ. Treatment of acute pandysautonomia with intravenous immunoglobulin. J Neurol Neurosurg Psychiatry 1997;62:529-31.
47. Smit AA, Vermeulen M, Koelman JH, et al. Unusual recovery from acute panautonomic neuropathy after immunoglobulin therapy. Mayo Clin Proc 1997;72:333-5.
48. Müller-Vahl KR, Müller-Vahl HG. Idiopathische autonome Neuropathie. Eine differentialdiagnostisch wichtige Erkrankung. Dtsch Med Wochenschr 1998;123:1343-6.
49. Nagasaka T, Togashi S, Nitta K, et al. A case of acute autonomic neuropathy. J Auton Nerv Syst 1998;74:199-200.
50. Nagasaka T, Togashi S, Amino A, et al. Idiopathic autonomic neuropathy associated with esophageal dilatation. J Neurol 2000;247:215-7.
51. Quan D, Rich MM, Bird SJ. Acute idiopathic dysautonomia: electrophysiology and response to intravenous immunoglobulin. Neurology 2000;54:770-1.
52. Colan RV, Snead OC III, Oh SJ, et al. Acute autonomic and sensory neuropathy. Ann Neurol 1980;8:441-4.
53. Edelman J, Gubbay SS, Zilko PJ. Acute pandysautonomia due to mixed connective tissue disease. Aust N Z J Med 1981;11:68-70.
54. Fujii N, Tabira T, Shibasaki H, et al. Acute autonomic and sensory neuropathy associated with elevated Epstein-Barr virus antibody titre. J Neurol Neurosurg Psychiatry 1982;45:656-8.
55. Lin SH. Acute pandysautonomia. Chin J Neurol Psychiat 1991;24:373-5.
56. Engstrom JW, Olney RK. Acute autonomic and sensory neuropathy. Muscle Nerve 1992;15:1181-2.
57. Pavesi G, Gemignani F, Macaluso GM, et al. Acute sensory and autonomic neuropathy: possible association with Coxsackie B virus infection. J Neurol Neurosurg Psychiatry 1992;55:613-5.
58. Yasuda T, Sobue G, Ito T, et al. Acute autonomic and sensory neuropathy. A case report with special reference to recovery from autonomic and sensory symptoms. J Auton Nerv Syst 1993;45:267.
59. Yasuda T, Sobue G, Mokuno K, et al. Clinico-pathophysiological features of acute autonomic and sensory neuropathy: a long-term follow-up study. J Neurol 1995;242:623-8.
60. Adachi H, Mukai E, Okuda S, et al. [A severe case of acute autonomic and sensory neuropathy.] Clin Neurol (Tokyo) 1998;38:663-8.
61. Kurokawa K, Noda K, Mimori Y, et al. A case of pandysautonomia with associated sensory ganglionopathy. J Neurol Neurosurg Psychiatry 1998;65:278-9.
62. Rolando S, Schinardi A, Bossolino C, et al. Acute autonomic and sensory neuropathy in childhood. J Peripher Nerv Syst 1998;3:155.
63. Irioka T, Yamada M, Yamawaki M, et al. Acute autonomic and sensory neuropathy after interferon α-2b therapy for chronic hepatitis C. J Neurol Neurosurg Psychiatry 2001;70:408-10.
64. Takahashi T, Tamura M, Chida K, et al. [A case of acute autonomic, sensory and motor neuropathy (AASMN)-less favourable response of the autonomic dysfunctions to IVIg treatment.] Rinso Shinkeigaku 2004;44:643-7.
65. Vernino S, Low PA, Fealey RD, et al. Autoantibodies to ganglionic receptors in autoimmune autonomic neuropathies. N Engl J Med 2000;343:847-55.
66. Goldstein DS, Holmes C, Dendi R, et al. Pandysautonomia associated with impaired ganglionic neurotransmission and circulating antibody to the neuronal nicotinic receptor. Clin Auton Res 2002;12:281-5.
67. Klein CM, Vernino S, Lennon VA, et al. The spectrum of autoimmune autonomic neuropathies. Ann Neurol 2003;53:752-8.
68. Canton DD, Sharp NJ, Aguirre GD. Dysautonomia in a cat. J Am Vet Med Assoc 1988;192:1293-6.
69. Symonds HW, McWilliams P, Thompson H, et al. A cluster of cases of feline dysautonomia (Key-Gaskell syndrome) in a closed colony of cats. Vet Rec 1995;136:353-5.
70. Longshore RC, O'Brien DP, Johnson GC, et al. Dysautonomia in dogs: a retrospective study. J Vet Intern Med 1996;10:103-9.
71. Friedman SA, Feinberg R, Podalak E, et al. Pupillary abnormalities in diabetic neuropathy: a preliminary study. Ann Intern Med 1967;67:977-83.
72. Hreidarsson AB. Pupil motility in long-term diabetes. Diabetologia 1979;17:145-50.
73. Hreidarsson AB. Pupil size in insulin-dependent diabetes. Relationship to duration, metabolic control, and long-term manifestations. Diabetes 1982;31:442-8.
74. Namba K, Utsumi T, Kitazawa A. Diabetes mellitus and pupil. (A preliminary report.) Nippon Ganka Gakkai Zasshi 1980;84:398-405.
75. Pfeifer MA, Weinberg CR, Cook DL, et al. Autonomic neural dysfunction in recently diagnosed diabetic subjects. Diabetes Care 1984;7:447-53.
76. Rundles RW. Diabetic neuropathy. General review with report of 125 cases. Medicine 1945;24:111-60.
77. Smith SE, Smith SA, Brown PM, et al. Pupillary signs in diabetic autonomic neuropathy. BMJ 1978;2:924-7.
78. Smith SA. Horner's syndrome in diabetes mellitus. Diabet Med 1987;4:381.
79. Smith SA, Smith SE. Evidence for a neuropathic aetiology in the small pupil of diabetes mellitus. Br J Ophthalmol 1983;67:89-93.
80. Hayashi M, Ishikawa S. Pharmacology of pupillary responses in diabetics-correlative study of the responses and grade of retinopathy. Jpn J Ophthalmol 1979;23:65-72.
81. Boutros G, Insler MS. Reversible pupillary miosis during a hyperglycaemic episode: case report. Diabetologia 1984;27:50-1.
82. Hreidarsson AB. Acute, reversible autonomic nervous system abnormalities in juvenile insulin-dependent diabetes. A pupillographic study. Diabetologia 1981;20:475-81.
83. Fujii T, Ishikawa S, Uga S. Ultrastructure of iris muscles in diabetes mellitus. Ophthalmologica 1977;174:228-39.
84. Ishikawa S, Bensaoula Y, Uga S, et al. Electron microscopic study of iris nerves and muscles in diabetes. Ophthalmologica 1985;191:172-83.
85. Maloney WF, Younge BR, Moyer NJ. Evaluation of the causes and accuracy of pharmacological localization in Horner's syndrome. Am J Ophthalmol 1980;90:394-402.
86. Thompson HS. Diagnosing Horner's syndrome. Trans Sect Ophthalmol Am Acad Ophthalmol Otolaryngol 1977;83:840-2.
87. Pfeifer MA, Cook D, Brodsky J, et al. Quantitative evaluation of sympathetic and parasympathetic control of iris function. Diabetes Care 1982;5:518-28.
88. Huber MJ, Smith SA, Smith SE. Mydriatic drugs for diabetic patients. Br J Ophthalmol 1985;69:425-7.
89. Hreidarsson AB, Gundersen HJ. The pupillary response to light in type I (insulin dependent) diabetes. Diabetologia 1985;28:815-21.
90. Smith SA, Smith SE. Reduced pupillary light reflexes in diabetic autonomic neuropathy. Diabetologia 1983;24:330-2.
91. Voutilainen-Kaunisto R, Niskanen L, Uusitupa M, et al. Iris transluminance in type 2 diabetes. Acta Ophthalmol Scand 2002;80:64-8.
92. Lowenstein O, Loewenfeld IE. The pupil. In: Davson H, ed. The Eye. Vol 3. New York: Academic Press; 1969:255-337.
93. Gundersen HJ. An abnormality of the central autonomic nervous system in long-term diabetes. Absence of hippus. Diabetologia 1974;10:366.
94. Kyle RA, Greipp PR. Amyloidosis (AL). Clinical and laboratory features in 229 cases. Mayo Clin Proc 1983;58:665-83.
95. Trotter JL, Engel WK, Ignaczak FI. Amyloidosis with plasma cell dyscrasia. An overlooked cause of adult onset sensorimotor neuropathy. Arch Neurol 1977;34:209-14.
96. Frewin DB, Gilmore HR, Ho JQ, et al. Clinical, physiological and pathological observations in a case of progressive autonomic nervous system degeneration associated with Holmes-Adie syndrome and peripheral neuropathy. Aust Ann Med 1968;17:141-7.
97. Gaan D, Mahoney MP, Rowlands DJ, et al. Postural hypotension in amyloid disease. Am Heart J 1972;84:395-400.
98. Horder JM, Treip CS. Primary amyloidosis with involvement of the peripheral nervous system. Neuropathol Appl Neurobiol 1977;3:297-302.
99. McGill NW, Tuck R, Hassall JE. Severe autonomic neuropathy in amyloidosis secondary to rheumatoid arthritis. Aust N Z J Med 1986;16:705-7.
100. Castleman B, Mallory TB, Towne VW. Case records of the Massachusetts General Hospital. N Engl J Med 1951;245:736-41.
101. Macoul KL, Winter FC. External ophthalmoplegia secondary to systemic amyloidosis. Arch Ophthalmol 1968;79:182-4.
102. Brownstein MH, Elliott R, Helwig EB. Ophthalmologic aspects of amyloidosis. Am J Ophthalmol 1970;69:423-30.
103. Goebel HH, Friedman AH. Extraocular muscle involvement in idiopathic primary amyloidosis. Am J Ophthalmol 1971;71:1121-7.
104. Raflo GT, Farrell TA, Sioussat RS. Complete ophthalmoplegia secondary to amyloidosis associated with multiple myeloma. Am J Ophthalmol 1981;92:221-4.
105. Sandgren O. Ocular amyloidosis, with special reference to the hereditary forms with vitreous involvement. Surv Ophthalmol 1995;40:173-96.
106. Duke JR, Paton D. Primary familial amyloidosis: ocular manifestations with histopathologic observations. Trans Am Ophthalmol Soc 1965;63:146-64.
107. Knowles DM II, Jakobiec FA, Rosen M, et al. Amyloidosis of the orbit and adnexae. Surv Ophthalmol 1975;19:367-84.
108. Lessell S, Wolf PA, Benson MD, et al. Scalloped pupils in familial amyloidosis. N Engl J Med 1975;293:914-5.
109. Kelly JJ Jr, Kyle RA, O'Brien PC, et al. The natural history of peripheral neuropathy in primary systemic amyloidosis. Ann Neurol 1979;6:1-7.
110. de Navasquez S, Treble HA. A case of primary generalised amyloid disease with involvement of the nerves. Brain 1938;61:116-28.
111. Chambers RA, Medd WE, Spencer H. Primary amyloidosis, with special reference to involvement of the nervous system. Q J Med 1958;27:207-26.
112. Burns RJ, Downey JA, Frewin DB, et al. Autonomic dysfunction with orthostatic hypotension. Aust N Z J Med 1971;1:15-21.
113. Wong VG, McFarlin DE. Primary familial amyloidosis. Arch Ophthalmol 1967;78:208-13.
114. Witschel H, Mobius W. Augenveränderungen bei generalisierter Amyloidose. Klin Monatsbl Augenheilkd 1974;165:610-6.
115. Davies DR, Smith SE. Pupil abnormality in amyloidosis with autonomic neuropathy. J Neurol Neurosurg Psychiatry 1999;67:819-22.
116. Shy GM, Drager GA. A neurological syndrome associated with orthostatic hypotension: a clinical-pathologic study. Arch Neurol 1960;2:511-27.
117. Thomas JE, Schirger A. Idiopathic orthostatic hypotension. A study of its natural history in 57 neurologically affected patients. Arch Neurol 1970;22:289-93.
118. Thapedi IM, Ashenhurst EM, Rozdilsky B. Shy-Drager syndrome. Report of an autopsied case. Neurology 1971;21:26-32.
119. Bannister R, Oppenheimer DR. Degenerative diseases of the nervous system associated with autonomic failure. Brain 1972;95:457-74.
120. Meyer JS, Shimazu K, Fukuuchi Y, et al. Cerebral dysautoregulation in central neurogenic orthostatic hypotension (Shy-Drager syndrome). Neurology 1973;23:262-73.
121. Rosen J, Brown SI. New ocular signs in Shy-Drager syndrome. Am J Ophthalmol 1974;78:1032-3.
122. Khurana RK, Nelson E, Azzarelli B, et al. Shy-Drager syndrome: diagnosis and treatment of cholinergic dysfunction. Neurology 1980;30:805-9.
123. Micieli G, Tassorelli C, Martignoni E, et al. Further characterization of autonomic involvement in multiple system atrophy: a pupillometric study. Funct Neurol 1995;10:273-80.
124. Sobue G, Terao S, Kachi T, et al. Somatic motor efferents in multiple system atrophy with autonomic failure: a clinico-pathological study. J Neurol Sci 1992;112:113-25.
125. Furukawa T, Toyokura Y. Alternating Horner syndrome. Arch Neurol 1974;30:311-3.
126. Nirankari VS, Khurana RK, Lakhanpal V. Ocular manifestations of Shy-Drager syndrome. Ann Ophthalmol 1982;14:635-8.
127. Tan E, Kansu T, Saygi S, et al. Alternating Horner's syndrome. A case report and review of the literature. J Neuroophthalmol 1990;10:19-22.
128. Rubenstein AE, Yahr MD. Adult onset autonomic dysfunction coexistent with familial dysautonomia in a consanguineous family. Neurology 1977;27:168-70.
129. Galassi G, Nemni R, Baraldi A, et al. Peripheral neuropathy in multiple system atrophy with autonomic failure. Neurology 1982;32:1116-21.
130. Sima AA, Caplan M, D'Amato CJ, et al. Fulminant multiple system atrophy in a young adult presenting as motor neurone disease. Neurology 1993;43:2031-5.
131. Bradbury S, Eggleston C. Postural hypotension. A report of three cases. Am Heart J 1925;1:73-86.
132. Kontos HA, Richardson DW, Norvel JE. Norepinephrine depletion in idiopathic orthostatic hypotension. Ann Intern Med 1975;82:336-41.
133. Polinsky RJ, Kopin IJ, Ebert MH, et al. Pharmacologic distinction of different orthostatic hypotension syndromes. Neurology 1981;31:1-7.
134. Dotson R, Ochoa J, Marchettini P, et al. Sympathetic neural outflow directly recorded in patients with primary autonomic failure: clinical observations, microneurography, and histopathology. Neurology 1990;40:1079-85.
135. Sakakibara R, Hattori T, Uchiyama T, et al. Micturitional disturbance in pure autonomic failure. Neurology 2000;54:499-501.
136. Mitsui T, Kawai H, Taguchi E, et al. Autonomic hyperreflexia in pure progressive autonomic failure. A case report. Neurology 1993;43:1823-5.
137. Beallo A. Bilateral tonic pupils, ptosis and myasthenic syndrome associated with oat cell carcinoma of the lung. Report of a case. Trans Pac Coast Oto Ophthal Soc Annu Meet 1965;46:89-102.
138. Rubenstein AE, Horowitz SH, Bender AN. Cholinergic dysautonomia and Eaton-Lambert syndrome. Neurology 1979;29:720-3.
139. O'Neill JH, Murray NM, Newsom-Davis J. The Lambert-Eaton syndrome. A review of 50 cases. Brain 1988;111:577-96.
140. Barkhaus PE, Rubenfeld M. Lambert-Eaton myasthenic syndrome with external ophthalmoplegia. Ann Neurol 1990;28:270.
141. Clark CV, Newsom-Davis J, Sanders MD. Ocular autonomic nerve function in Lambert-Eaton myasthenic syndrome. Eye 1990;4:473-81.
142. Muchnik S, Losavio AS, Vidal A, et al. Long-term follow-up of Lambert-Eaton syndrome treated with intravenous immunoglobulin. Muscle Nerve 1997;20:674-8.
143. Wirtz PW, De Keizer RJ, de Visser M, et al. Tonic pupils in Lambert-Eaton myasthenic syndrome. Muscle Nerve 2001;24:444-5.
144. Burns TM, Russell JA, LaChance DH, et al. Oculobulbar involvement is typical with Lambert-Eaton myasthenic syndrome. Ann Neurol 2003;53:270-3.
145. Fagius J, Westerberg CE, Olsson Y. Acute pandysautonomia and severe sensory deficit with poor recovery. A clinical, neurophysiological and pathological case study. J Neurol Neurosurg Psychiatry 1983;46:725-33.
146. Khurana RK, Koski CL, Mayer RF. Autonomic dysfunction in Lambert-Eaton myasthenic syndrome. J Neurol Sci 1988;85:77-86.
147. West CE, Repka MX. Tonic pupils associated with neuroblastoma. J Pediatr Ophthalmol Strabismus 1992;29:382-3.
148. Lambert SR, Yang LL, Stone C. Tonic pupil associated with congenital neuroblastoma, Hirschsprung disease, and central hypoventilation syndrome. Am J Ophthalmol 2000;130:238-40.
149. Mamdani MB, Walsh RL, Rubino FA, et al. Autonomic dysfunction and Eaton Lambert syndrome. J Auton Nerv Syst 1985;12:315-20.
150. Waterman SA. Autonomic dysfunction in Lambert-Eaton myasthenic syndrome. Clin Auton Res 2001;11:145-54.
151. Brain L, Wilkinson M. Subacute cerebellar degeneration associated with neoplasms. Brain 1965;88:465-78.
152. Schuffler MD, Baird HW, Fleming CR, et al. Intestinal pseudo-obstruction as the presenting manifestation of small-cell carcinoma of the lung. Ann Intern Med 1983;98:129-34.
153. Oh SJ, Dropcho EJ, Claussen GC. Anti-Hu-associated paraneoplastic sensory neuronopathy responding to early aggressive immunotherapy: report of two cases and review of literature. Muscle Nerve 1997;20:1576-82.
154. Casas Parera I, Fischman D, Paz L, et al. [Paraneoplastic neuropathy with positive anti-Hu.] Medicina (B Aires) 1998;58:197-201.
155. Maitland CG, Scherokman BJ, Schiffman J, et al. Paraneoplastic tonic pupils. J Clin Neuro-Ophthal 1985;5:99-104.
156. Eggers C, Hagel C, Pfeiffer G. Anti-Hu-associated paraneoplastic sensory neuropathy with peripheral nerve demyelination and microvasculitis. J Neurol Sci 1998;155:178-81.
157. Bell TAG. Adie's tonic pupil in a patient with carcinomatous neuromyopathy. Arch Ophthalmol 1986;104:331-2.
158. van Lieshout JJ, Wieling W, van Montfrans GA, et al. Acute dysautonomia associated with Hodgkin's disease. J Neurol Neurosurg Psychiatry 1986;49:830-2.
159. Bruno MK, Winterkorn JM, Edgar MA, et al. Unilateral Adie pupil as sole ophthalmic sign of anti-Hu paraneoplastic syndrome. J Neuroophthalmol 2000;20:248-9.
160. Muller NG, Prass K, Zschenderlein R. Anti-Hu antibodies, sensory neuropathy, and Holmes-Adie syndrome in a patient with seminoma. Neurology 2005;64:164-5.
161. Attwood W, Poser CM. Neurological complications of Sjögren's syndrome. Neurology 1961;11:1034-41.
162. Bachmeyer C, Zuber M, Dupont S, et al. Adie syndrome as the initial sign of primary Sjögren syndrome. Am J Ophthalmol 1977;123:691-2.
163. Gudesblatt M, Goodman AD, Rubenstein AE, et al. Autonomic neuropathy associated with autoimmune disease. Neurology 1985;35:261-4.
164. Gemignani F, Manganelli P, Pavesi G, et al. Polyneuropathy in Sjögren's syndrome. A case of prevalently autonomic neuropathy with tonic pupil and hypohidrosis. Funct Neurol 1988;3:337-48.
165. Mellgren SI, Conn DL, Stevens JC, et al. Peripheral neuropathy in primary Sjögren's syndrome. Neurology 1989;39:390-4.
166. Griffin JW, Cornblath DR, Alexander E, et al. Ataxic sensory neuropathy and dorsal root ganglionitis associated with Sjögren's syndrome. Ann Neurol 1990;27:304-15.
167. Kaplan JG, Rosenberg R, Reinitz E, et al. Invited review: peripheral neuropathy in Sjögren's syndrome. Muscle Nerve 1990;13:570-9.
168. Waterschoot MP, Guerit JM, Lambert M, et al. Bilateral tonic pupils and polyneuropathy in Sjögren's syndrome: a common pathophysiological mechanism? Eur Neurol 1991;31:114-6.
169. Kumazawa K, Sobue G, Yamamoto K, et al. Segmental anhidrosis in the spinal dermatomes in Sjögren's syndrome-associated neuropathy. Neurology 1993;43:1820-3.
170. Vetrugno R, Liguori R, Cevoli S, et al. Adie's tonic pupil as a manifestation of Sjögren's syndrome. Ital J Neurol Sci 1997;18:293-5.
171. Tajima Y, Tsukishima E, Sudo K, et al. [A case of Sjögren syndrome associated with multiple mononeuritis and dysautonomia including bilateral tonic pupils.] Brain Nerve 1997;49:825-8.
172. Goto H, Matsuo H, Fukudome T, et al. Chronic autonomic neuropathy in a patient with primary Sjögren's syndrome. J Neurol Neurosurg Psychiatry 2000;69:135.
173. Kennett RP, Harding AE. Peripheral neuropathy associated with the sicca syndrome. J Neurol Neurosurg Psychiatry 1986;49:90-2.
174. Wright RA, Grant IA, Low PA. Autonomic neuropathy associated with sicca complex. J Auton Nerv Syst 1999;75:70-6.
175. Bacman S, Perez Leiros C, Sterin-Borda L, et al. Autoantibodies against lacrimal gland M3 muscarinic acetylcholine receptors in patients with primary Sjogren's syndrome. Invest Ophthalmol Vis Sci 1998;39:151-6.
176. Waterman SA, Gordon TP, Rischmueller M. Inhibitory effects of muscarinic receptor autoantibodies on parasympathetic neurotransmission in Sjogren's syndrome. Arthritis Rheum 2000;43:1647-54.
177. Riley CM, Day RL, Greeley D, et al. Central autonomic dysfunction with defective lacrimation. Pediatrics 1949;3:468-78.
178. Smith AA, Dancis J, Breinin G. Ocular responses to autonomic drugs in familial dysautonomia. Invest Ophthalmol 1965;4:358-61.
179. Solitaire GB, Cohen GS. Peripheral autonomic nervous system lesions in congenital or familial dysautonomia (Riley-Day syndrome). Neurology 1965;15:321-7.
180. Shinebourne E, Turner P, Sneddon JM. Evidence for autonomic denervation in familial dysautonomia, the Riley-Day syndrome. BMJ 1967;4:91-2.
181. Goldberg MF, Payne JW, Brunt PW. Ophthalmological studies of familial dysautonomia. The Riley-Day syndrome. Arch Ophthalmol 1968;80:732-43.
182. Liebman SD. Riley-Day syndrome: long-term ophthalmologic observations. Trans Am Ophthalmol Soc 1968;66:95-116.
183. Brunt PW, McKusick VA. Familial dysautonomia: a report of genetic and clinical studies, with a view of the literature. Medicine 1970;49:343-74.
184. Mahloudji M, Brunt PW, McKusick VA. Clinical neurological aspects of familial dysautonomia. J Neurol Sci 1970;11:383-95.
185. Aguayo AJ, Nair CP, Bray GM. Peripheral nerve abnormalities in the Riley-Day syndrome. Findings in a sural nerve biopsy. Arch Neurol 1971;24:106-16.
186. Francois J. The Riley-Day syndrome: familial dysautonomy, central autonomic dysfunction. Ophthalmologica 1977;174:20-34.
187. Levine SL, Manniello RL, Farrell PM. Familial dysautonomia: unusual presentation in an infant of non-Jewish ancestry. J Pediatr 1977;90:79-81.
188. Korczyn AD, Rubenstein AE, Yahr MD, et al. The pupil in familial dysautonomia. Neurology 1981;31:628-9.
189. Tervo T, Setala K, Tervo K, et al. Familial dysautonomia (Riley-Day syndrome) in Finnish twins. J Neuroophthalmol 1993;13:45-9.
190. Riley CM, Moore RH. Familial dysautonomia differentiated from related disorders. Case reports and discussions of current concepts. Pediatrics 1966;37:435-46.
191. Dunnington JH. Congenital alacrima in familial autonomic dysfunction. Arch Ophthalmol 1954;52:925-31.
192. Gadoth N, Schlaen N, Maschkowski D, et al. The pupil cycle time in familial dysautonomia: further evidence for denervation supersensitivity. Metab Pediat Syst Ophthalmol 1983;7:131-4.
193. Dütsch M, Hilz MJ, Rauhut U, et al. Sympathetic and parasympathetic dysfunction in familial dysautonomia. J Neurol Sci 2002;195:77-83.
194. Robertson D, Goldberg MR, Onrot J, et al. Isolated failure of autonomic noradrenergic neurotransmission. Evidence for impaired β-hydroxylation of dopamine. N Engl J Med 1986;314:1494-7.
195. Man in't Veld AJ, Boomsma F, Moleman P, et al. Congenital dopamine-β-hydroxylase deficiency. A novel orthostatic syndrome. Lancet 1987;1:183-8.
196. Man in't Veld A, Boomsma F, Lenders J, et al. Patients with congenital dopamine β-hydroxylase deficiency. A lesson in catecholamine physiology. Am J Hypertens 1988;1:231-8.
197. Biaggioni I, Goldstein DS, Atkinson T, et al. Dopamine-β-hydroxylase deficiency in humans. Neurology 1990;40:370-3.
198. Mathias CJ, Bannister RB, Cortelli P, et al. Clinical, autonomic and therapeutic observations in two siblings with postural hypotension and sympathetic failure due to an inability to synthesise noradrenaline from dopamine because of a deficiency of dopamine beta hydroxylase. Q J Med 1990;75:617-33.
199. Thompson JM, O'Callaghan CJ, Kingwell BA, et al. Total norepinephrine spillover, muscle sympathetic nerve activity and heart-rate spectral analysis in a patient with dopamine β-hydroxylase deficiency. J Auton Nerv Syst 1995;55:198-206.
200. Kazakos DC, Smith SE, Bron AJ. The pupil response to pilocarpine nitrate (0.125%) in dry eye patients. Ophthalmic Res 2001;33(suppl 1):108.
201. Sakakibara R, Hirano S, Asahina M, et al. Primary Sjögren's syndrome presenting with generalized autonomic failure. Eur J Neurol 2004;11:635-8.
202. Ramirez C, De Seze J, Stojkovic T, et al. Pure subacute pandysautonomia: an assessment of treatment with intravenous polyvalent immunoglobulins. Rev Neurol (Paris) 2004;160:939-41.
© 2006 Lippincott Williams & Wilkins, Inc.