Analysis Of Clinical And Pathological Features Of Ross Syndrome

Background Ross syndrome is a rare sporadic neurodegenerative autonomic disorder characterized by pan autonomic failure without other features of neurologic dysfunctions,which has the clinical triad of segmental anhidrosis,tonic pupil and areflexia.Neuropathological studies have shown that Ross syndrome was due to selective loss of cholinergic neurons in the peripheral autonomic nervous system: injury to the sudomotor sympathetic cholinergic bundles within eccrine glands led to anhidrosis;Tonic pupils were the post-ganglionic denervation of cholinergic fibers between the ciliary ganglion and the iris sphincter muscle;Depression of deep tendon reflexes is due to dorsal root ganglionic degeneration and spinal interneuron loss.However,the mechanism of selective loss of cholinergic neurons in patients with Ross syndrome remain unclear,so there is no specific treatment for the mechanism and etiology and clinical treatment is mainly symptomatic.Therefore,it is vital to investigate the mechanisms and causes of cholinergic neuron degeneration,which may be a breakthrough for the therapy of Ross syndrome.To analyze and summarize thefeatures of symstoms,accessory examination and pathophysiological in Ross syndrome patients,to further explore the pathogenesis and to improve clinicians' recognition of Ross syndrome.MethodCollecting all patients diagnosed with Ross syndrome between September 2016 and December 2018,three patients were hospitalized in Department of Neurology,First Affiliated Hospital of Zhengzhou University,who were diagnosed as Ross syndrome by two experts at the same time.The clinical data,blood autoimmune markers,thermoregulatory sweat test,electrophysiological test,digital infrared thermal imaging,brain magnetic resonance,skin,gastrointestinal tract and urinary tract biopsies were collected.The key word "Ross syndrome" was input on PubMed to retrieve the relevant literature of Ross syndrome.The clinical manifestations,accessory examinations and skin biopsies were analyzed.ResultsThere were two males and one female among the patients,who presented with unilateral anhidrosis and tonic pupil.Two patients also showed gastrointestinal paresis,the another suffered urinary incontinence and impotence or sexual dysfunction.Their blood tests and physical examination were normal.However,their neurological examination revealed bilateral hyporeflexia.Additionally,TST confirmed segmental anhidrosis involved in their body surface in agreement with their main complaints.DITI revealed that the mean skin temperature of the anhidrosis area was higher than that of hyperhidrosis area.Biopsies of skin,gastrointestinal tract and bladder showed decreased cholinergic nerve fibers and deposition of pathological?-Syn inclusion bodies.Review the 24 Ross syndrom case literature,including 14 males and 10 females.The age of onset is between 22 and 63 years old.Incidence of Ross syndrome was equal in both males(n=14,58%)and females(n=10,42%),and the average age of onset was 26 years old.The most common presenting complaint was hyperhidrosis and was present in 62.5%(n=15)of patients,which was followedby hypohidrosis,and 29%(n=7)of patients complained about the reduction of sweating in a specific part of the body.Although 14 patients(58.3%)had clinical features of segmental anhidrosis,tonic pupils,and areflexia establishing the diagnosis of complete Ross,10(41.7%)had only two components of the triad,suggestive of an incomplete Ross syndrome.Electrophysiological studies were done in 19 of the 24 patients,among which sympathetic skin response(SSR)was absent in 89%(n=17)patients.6%(n=1)of patients presented nomal latency with low amplitude of H reflexes,Which was elicited in 94%(n=18)of patients.Skin biopsy was performed on 17 patients,82%(n=14)0f whom showed no inflammatory infiltration and immune complex deposition around sweat glands,and significantly decreased PGP9.5-positive nerve fibers,and vasoactive intestinal peptide-immunoreactive(VIP-ir)nerve fibers,18%(n=3)was normal.Conclusion1.Pathological ?-syn inclusion bodies deposits in the skin,gastrointestinal and bladder tract in Ross syndrome patients,Ross syndrome may be a new subtype of?-synucleinopathy.2.Degenerative changes resulting from the aggregations of ?-Syn insoluble inclusions in diverse autonomic nerve fibers may be the Pathological basis of major clinical phenotypes,such as segmental anhidrosis,tonic pupil and areflexia for Ross syndrome.