[Dysautonomic syndrome of the face with Harlequin sign and syndrome: Three new cases and a review of the literature]. / Syndromes dysautonomiques du visage avec signe et syndrome d'Harlequin : étude de trois cas et revue de la littérature.

INTRODUCTION: Harlequin phenomenon is characterized by a strictly unilateral erythrosis of the face with flushing and hyperhydrosis, and controlaterally a pale anhydrotic aspect. This syndrome can occur alone or associated to other dysautonomic phenomena such as Horner syndrome, Adie syndrome or Ross syndrome. PATIENTS AND METHODS: We report three cases: two patients presented a Harlequin sign, associated with Horner syndrome for one and Ross syndrome for the second. The etiologic investigation was normal, allowing recognizing the idiopathic nature of the disorder. For the third patient, Harlequin syndrome was observed in a neoplastic context due to breast cancer, metastatic dissemination, and bone metastases involving the right side of the T2 body. DISCUSSION: We reviewed the literature: 108 cases have been described. This syndrome occurred alone in 48 patients and was associated with other dysautonomic syndromes such as Horner syndrome in 38 patients, Holmes Adie syndrome in six, and Ross syndrome in six; both Ross and Holmes Adie syndrome were associated five cases and associations were not reported in five patients. The pathophysiological mechanisms of this autonomic cranial neuropathy, the possible etiologies, and therapeutic management were discussed. CONCLUSION: Harlequin phenomenon with flushing and unilateral hyperhydrosis is rare, occurring alone or in combination with other autonomic syndromes of the face. Idiopathic in two-thirds of cases, Harlequin phenomenon does not require specific treatment; sympathectomy may be discussed in the severe cases with a significant social impact.

Holmes-Adie syndrome associated with high altitude pulmonary edema and low chemo-responsiveness to hypoxia.

A 63-year-old patient with Holmes-Adie syndrome presented an altered peripheral chemoreflex and suffered from high altitude pulmonary edema, suggesting an alteration of sensitive afferent fibers from the peripheral chemoreceptors. Chemo-responsiveness to hypoxia should be explored before any exposure to moderate altitude in Holmes-Adie patients.

Holmes-Adie syndrome, autoimmune hepatitis and celiac disease: a case report.

A 35-year-old female patient presented with the following symptoms of Holmes-Adie syndrome: photophobia,enlargement of the left pupil unresponsive to light, Achilles areflexia. The pilocarpine test was positive. No tumor or other neurological abnormality was found. She had a 19-year history of autoimmune hepatitis. Flares up were observed following each 3 deliveries. At age of 31 she presented with diarrhea and weight loss. Abdominal tumor was detected by ultrasound. The surgically removed tumor was histologically a benign mesenteric multicystic lymphangioma.Simultaneously, celiac disease was diagnosed.Gluten-free diet resulted in a significant improvement of celiac disease,but not of autoimmune hepatitis. Autonomic neuropathy was proven by standard cardiovascular tests. The patient was a homozygous carrier for HLA DQ2 antigen characteristic for celiac disease and heterozygous for HLA DR3 B8 frequent in autoimmune liver diseases. Our novel observation on association of Holmes-Adie syndrome with autoimmune hepatitis and celiac disease is suggestive for a common immunological background for all three entities present in a patient with mesenteric multicystic lymphangioma.

Loss of facial sweating and flushing in Holmes-Adie syndrome.

We investigated pupillary responses to parasympathetic (pilocarpine) and sympathetic agents (tyramine, cocaine, and phenylephrine) in a 51-year-old woman with tonic pupils, loss of muscle stretch reflexes in the limbs, and hemifacial loss of sweating and flushing (Ross' syndrome). A smaller pupillary response to tyramine and cocaine eyedrops on the symptomatic side indicated that outflow was disrupted in the postganglionic section of the ocular sympathetic pathway. A greater response to phenylephrine eyedrops on this side was consistent with denervation supersensitivity to adrenergic agents. Loss of thermoregulatory sweating and flushing and emotional blushing in the forehead, cheek, and chin indicated that sympathetic disruption was proximal to the bifurcation of the common carotid artery, probably in the superior cervical ganglion. A similar degenerative process may be responsible for loss of muscle stretch reflexes, tonic pupils, and other autonomic disturbances in Ross' syndrome.

Ciliary muscle dysfunction in Adie's syndrome.

Ciliary muscle function in patients with Adie's syndrome was studied retrospectively in 122 patients and prospectively in 17 patients. When a careful history was taken, two thirds of the patients had ciliary muscle-related symptoms. Most of the patients with Adie's syndrome had a moderate accomodative paresis, but there was a strong tendency for the ciliary muscle to recover with time. Many patients showed a tonicity of accommodation, especially those who had had the condition for several years. Astigmatism could be induced with accommodation in one third of patients. This may be related to segmental paralysis of the ciliary muscle. Seventy-three percent of the patients showed supersensitivity of the ciliary muscle in the involved eye, when both eyes were treated with a mixture of 0.25% pilocarpine hydrochloride and hydroxypropyl methylcellulose (Isopto Carpine). This may be a clinical aid in diagnosing Adie's syndrome. Two patients were found to have bilateral ciliary muscle dysfunction but only unilateral pupillary abnormalities. These two patients may have had a "pupil-sparing" Adie's syndrome.

Spontaneous cyclic segmental sphincter spasms in an Adie's tonic pupil.

A 43-year-old woman with bilateral Adie's tonic pupils had a segment of one iris sphincter that contracted spontaneously every few seconds, but was not influenced by light, near vision, or eye movements.

Adie syndrome: evidence for refractive error and accomodative asymmetry as the cause of amblyopia.

PURPOSE: To report objective changes in accommodation in a child with Adie syndrome. METHODS: A child aged 2 years 10 months when initially examined was found to have good visual acuity in both eyes, a low degree of hypermetropia (isometropic), and Adie pupil presumed to be caused by chicken pox that had occurred 2 months earlier. Amblyopia developed but responded well to treatment, which involved correction of the refractive error and occlusion therapy. Objective changes in the refraction of the eye were measured on the Canon R1 autorefractor at 3.8 m and 33 cm. RESULT: The degree of accommodation in the affected eye when both eyes were open was markedly reduced. CONCLUSION: The presence of isometropic hypermetropia, which remains uncorrected when Adie syndrome is present, can lead to the development of amblyopia in a child.

Idiopathic unilateral hyperhidrosis with Holmes-Adie syndrome: case report.

Hyperhidrosis is a disease that is characterized by excessive sweating due to hyperactivation of eccrine sweat glands. It may be localized or generalized form. Holmes-Adie syndrome is an idiopathic disease with unilateral pupil dilatation and loss of deep tendon reflexes. We present a 37-year-old female patient diagnosed with unilateral hyperhidrosis coincident with Holmes-Adie syndrome because of this unusual presentation.

[An unusual case of pseudotabetic arthropathy]. / Considerazioni su un raro caso di artropatia pseudotabetica.

After a brief introduction on Adie's disease, or pseudotabes, a rare case of pseudotabetic arthropathy which, in addition to the classical signs of Adie's syndrome, presented signs of a recurrent arthrosynovitis of the knee, is reported. This rare syndrome should be borne in mind in differential diagnosis with recurrent arthrosynovitis of other nature.

Adie's syndrome as a cause of amblyopia.

Adie's syndrome comprises a tonic pupil, which may be associated with impairment of accommodation, in the presence of diminished or absent deep tendon reflexes. We report a case of a 4-year-old boy with Adie's syndrome in which latent hypermetropia was made manifest by accommodative paresis and resulted in reversible amblyopia.

[Surgical treatment for compensatory hyperhidrosis in Adie syndrome]. / Tratamiento quirúrgico de la hiperhidrosis compensadora en el síndrome de Adie.

Ross syndrome is characterized by a triad of tonic pupil, areflexia and segmental hypohidrosis. Hypohidrosis may be accompanied by contralateral hyperhidrosis, probably due to a compensatory mechanism. We report a case of Ross syndrome with socially disabling left-sided hyperhidrosis. Sympathectomy of the second and third thoracic ganglia was performed with satisfactory results. With excellent results in primary hyperhidrosis and very low morbidity, thoracic sympathectomy is the definitive treatment for hyperhidrosis.

On the cause of tendon areflexia in the Holmes-Adie syndrome.

A case of Holmes-Adie syndrome was studied clinically and electrophysiologically. A total loss of tendon reflexes was observed in upper and lower limbs. The main electrophysiological finding was a marked increase of the central conduction time after stimulation of peroneal and tibial nerves. Motor evoked potentials in soleus muscle after transcranial magnetic stimulation showed normal threshold and latencies. We suggest that tendon areflexia could be a consequence of a dysfunction of somatosensory large diameter afferent fibres at the spinal level.

[Two families of Charcot-Marie-Tooth disease with Adie's pupil, axonal neuropahy and the Thr124Met mutation in the peripheral myelin protein zero gene].

We reported two families of Charcot-Marie-Tooth disease (CMT) with Thr124Met mutation in the peripheral myelin protein zero (MPZ). The clinical features of the proband patients of both families showed Adie's pupil, severe sensory dominant neuropathy in lower extremities, and axonal changes in sural nerve biopsies and nerve conduction studies. Muscle atrophy and weakness was mild in the lower legs, while sensory impairment was marked. The proband patient of family 1 had four symptomatic siblings and one of them showed Adie's pupil. The elderly daughter of the proband of family 2 showed Adie's pupil and younger daughter showed photophobia. The biopsied sural nerves of both proband patients revealed prominent axonal sprouting, and sub-perineurial edema and mild fascicular enlargement. Segmental demyelination was not frequent in teased fiber assessment. The present two family cases strongly suggest that this MPZ gene mutation (Thr124Met) could be present among the patients with CMT type 2, axonal form. Furthermore, the patients showing sensory neuropathy and Adie's pupil may need to be reexamined with this mutation. It is also necessary to reassess genotype-phenotype correlation in CMT patients particularly in reference to type 1 and type 2.

[Small fiber dysfunction in peripheral neuropathies]. / Afectación de fibras finas en la patología del nervio periférico.

INTRODUCTION: Disfunction of thin myelinated and unmyelinated fibers may appear isolated or in association with large-myelinated fibers lesion. Small-fiber neuropathy includes autonomic and sensory symptoms, most prominent of them thermo-algesic deficits. DEVELOPMENT AND CONCLUSION: In some acute neuropathies, small-fiber lesion is relatively pure, as in pandysautonomia, but it also appears in disorders with prominent somatic involvement, such as the Guillain-Barre syndrome, in which case autonomic symptoms worsens the prognosis. Small-fiber dysfunction is important in certain diseases that involve different components of the nervous system, like paraneoplastic syndromes and porphyria. Some drugs and toxic substances may damage thin myelinated and unmyelinated fibers. Nowadays, chronic idiopathic small-fiber neuropathy is diagnosed more frequently, because of the recent development of techniques that selectively evaluate this peripheral nerve component. Hereditary sensory and autonomic neuropathies can also be studied. Small-fiber dysfunction is very prominent in some diseases, e.g. diabetes mellitus and amyloidosis. In the pure autonomic failure, only the peripheral component of the autonomic nervous system is affected, and this feature is the key to make diagnosis versus multisystem atrophy. There are situations in which there is no clear deviation from normality, namely old age autonomic failure and orthostatic intolerance syndrome in which autonomic evaluation is mandatory.

[Tonic pupil and tendon areflexia: the Holmes-Adie's syndrome]. / Pupilla tonica e areflessia tendinea: la sindrome di Holmes-Adie.

The Holmes-Adie syndrome (HAS) is characterised by initially monolateral, then bilateral enlargement of the pupil with delayed responses to near vision and subsequent redilation, and absent tendon reflexes. The diameter of the affected pupil is oval or irregular, sometimes with spontaneous movements of the pupillary sphincter muscle. Reaction to light may require several minutes' exposure to bright light, as it does redilation after a prolonged stay in a dark room. The reaction to near vision is tonic and delayed, as the subsequent redilation. In 10% of cases there is a permanent failure of the pupil to react either to light or to near vision. Absence of deep tendon reflexes is acquired and permanent, most frequently involving the Achilles' tendon reflex. Loss of different degrees of ciliary and spinal ganglia neurons, without evidence of inflammatory findings, are the neuropathological data accounting for the clinical signs of HAS. Polyneuropathies of different origin can be complicated by a symptomatic form of HAS.

Complete Vogt-Koyanagi-Harada disease and Holmes-Adie syndrome: case report.

We report a 37-year-old woman with uveitic phase of Vogt Koyanagi Harada disease and tonic pupil, the tonic pupil persisted after other clinical features of this syndrome had disappeared; neurological evaluation shows absent knee and arm tendon reflexes and positive cholinergic supersensitivity test with Pilocarpine 0.125% confirming the diagnosis of Holmes Adie Syndrome.