Intranasal dexmedetomidine for adrenergic crisis in familial dysautonomia.

PURPOSE: To report the use of intranasal dexmedetomidine, an α2-adrenergic agonist for the acute treatment of refractory adrenergic crisis in patients with familial dysautonomia. METHODS: Case series. RESULTS: Three patients with genetically confirmed familial dysautonomia (case 1: 20-year-old male; case 2: 43-year-old male; case 3: 26-year-old female) received intranasal dexmedetomidine 2 mcg/kg, half of the dose in each nostril, for the acute treatment of adrenergic crisis. Within 8-17 min of administering the intranasal dose, the adrenergic crisis symptoms abated, and blood pressure and heart rate returned to pre-crises values. Adrenergic crises eventually resumed, and all three patients required hospitalization for investigation of the cause of the crises. CONCLUSIONS: Intranasal dexmedetomidine is a feasible and safe acute treatment for adrenergic crisis in patients with familial dysautonomia. Further controlled studies are required to confirm the safety and efficacy in this population.

Cyclic vomiting associated with excessive dopamine in Riley-day syndrome.

GOALS: To analyze the neurochemical profile during the recurrent attacks of nausea and vomiting in patients with Riley-day syndrome. BACKGROUND: One of the most disabling features of patients with Riley-day syndrome are recurrent attacks of severe nausea/retching/vomiting accompanied by hypertension, tachycardia, and skin flushing, usually triggered by emotional or other stresses. STUDY: We monitored blood pressure and heart rate and measured plasma catecholamines during typical dysautonomic crises triggered by emotionally charged situations. For comparison, measurements were repeated at follow-up after the symptoms had resolved and the patients were feeling calm and well. RESULTS: During a typical attack, patients were hypertensive and tachycardic. In all patients, circulating levels of norepinephrine (P < 0.002) and dopamine (P < 0.007) increased significantly. CONCLUSIONS: Activation of dopamine receptors in the chemoreceptor trigger zone may explain the cyclic nausea/retching/vomiting of patients with Riley-day syndrome.

Afferent baroreflex failure in familial dysautonomia.

BACKGROUND: Familial dysautonomia (FD) is due to a genetic deficiency of the protein IKAP, which affects development of peripheral neurons. Patients with FD display complex abnormalities of the baroreflex of unknown cause. METHODS: To test the hypothesis that the autonomic phenotype of FD is due to selective impairment of afferent baroreceptor input, we examined the autonomic and neuroendocrine responses triggered by stimuli that either engage (postural changes) or bypass (cognitive/emotional) afferent baroreflex pathways in 50 patients with FD and compared them to those of normal subjects and to those of patients with pure autonomic failure (PAF), a disorder with selective impairment of efferent autonomic neurons. RESULTS: During upright tilt, in patients with FD and in patients with PAF blood pressure fell markedly but the heart rate increased in PAF and decreased in FD. Plasma norepinephrine levels failed to increase in both groups. Vasopressin levels increased appropriately in patients with PAF but failed to increase in patients with FD. Head-down tilt increased blood pressure in both groups but increased heart rate only in patients with FD. Mental stress evoked a marked increase in blood pressure and heart rate in patients with FD but little change in those with PAF. CONCLUSION: The failure to modulate sympathetic activity and to release vasopressin by baroreflex-mediated stimuli together with marked sympathetic activation during cognitive tasks indicate selective failure of baroreceptor afference. These findings indicate that IKAP is critical for the development of afferent baroreflex pathways and has therapeutic implications in the management of these patients.

Familial dysautonomia's impact on quality of life in childhood, adolescence, and adulthood.

AIM: To evaluate the quality of life (QoL) of children, adolescents, and adults treated for familial dysautonomia (FD), a pervasive neurological disorder. METHODS: The Child Health Questionnaire was completed by parents of 71 patients, while an additional 74 patients completed the Short Form--36. RESULTS: FD imposed a greater physical than psychosocial burden on the child, while the young adults reported both mental and physical quality of life within the average range. Self-esteem was problematic and improved with age, while both groups reported lowering physical quality of life as they grew older, with worsening general health that limited their role at school or work. CONCLUSION: Younger FD patients should be closely monitored for lowered self-esteem and referred for counseling when appropriate, while physical and occupational therapy should be provided in advance of expected lowered physical QoL and role fulfillment with increasing age. This becomes important as the need for additional surgical interventions, such as fundoplication with gastrostomy or spinal fusion, contribute to lower physical functioning. Given the high degree of parental involvement required for the varied manifestations of this multisystem disorder, the need for continued parental assessment and psycho-education about this chronic medical illness is warranted.

Quantitative sensory testing of thermal and vibratory perception in familial dysautonomia.

Familial dysautonomia (FD) is an inherited disorder that is known to affect both sensory and autonomic functions as a result of incomplete neuronal development and progressive loss but the degree to which patients are affected differs greatly. To determine if quantitative vibration and thermal testing refined the assessment of severity, 23 familial dysautonomia patients were evaluated by clinical examination, measurements of median, peroneal and sural nerve conduction velocities (NCV), and assessment of vibration thresholds at two body sites and of warm and cold perception thresholds at 6 body sites using the method of limits. Data from 80 age-matched normal individuals provided control data for vibration and temperature thresholds. All familial dysautonomia patients had abnormal thermal thresholds. Vibration perception was abnormal in 20 patients. NCVs were slowed in 8 of 16 patients who agreed to be tested. Abnormalities in thermal thresholds are consistent with the reduction of small nerve fibers in familial dysautonomia Abnormal vibration thresholds might be due to disturbed conduction of vibratory impulse trains and reflect the degree to which the disorder is progressive. Vibration and thermal sensation testing were better accepted and provided more information than NCV regarding severity of disease.

Oro-dental self-mutilation in familial dysautonomia.

Orodental self-mutilation (ODSM) has not gained sufficient recognition in familial dysautonomia (FD). Among 38 patients with FD, ODSM was found in 14 (36.8%). ODSM may be due to peripheral neuropathy with insensibility to pain, which is characteristic of FD. Elimination of the sharp edges of teeth was found to be helpful.

Orthopaedic manifestations in congenitally insensate patients.

The spectrum of orthopaedic problems in eight congenitally insensate patients was reviewed. The conditions included congenital insensitivity to pain, Riley-Day syndrome, and Lesch-Nyhan syndrome. In each of these conditions, the patient has an abnormality of interpretation of painful stimuli or lacks normal pain avoidance, leading to self-inflicted damage. The orthopaedic problems and complications included fracture, self-mutilation, autoamputation, osteomyelitis, septic arthritis, Charcot joints, scoliosis, and dislocation. Effective management consists of early diagnosis and patient/parent education to prevent as many complications as possible. Fractures may be treated conservatively, while progressive scoliosis requires operative intervention. Osteomyelitis, septic arthritis, and Charcot joints require appropriate operative treatment.

Psychiatric aspects of acute pandysautonomia.

Five cases of acute pandysautonomia and one case of acute autonomic and sensory neuropathy are described with special reference to psychiatric symptoms. They originally presented as psychiatric disorders, such as hysterical neurosis, epilepsy, anorexia nervosa and hypochondriacal neurosis. Psychiatric symptoms arise from their autonomic nervous dysfunction and show emotional instabilities which are often regarded as hysterical overacting.

Behavioral effects of early deprivation of nerve growth factor: some similarities with familial dysautonomia.

Female rats immunized with mouse nerve growth factor develop an antibody (anti-NGF) which reaches offspring through the placenta and via the milk. Pups exposed to maternal anti-NGF have fewer dorsal root and sympathetic neurons. When the offspring are examined on a wide variety of behavioral tests, they exhibit severe deficits in response to stress (ulceration, corticosterone levels), and mild deficits on some sensory and cognitive tasks. Exploratory and motor functions, however, are relatively normal. The pathologic and behavioral profiles of the animals closely mimic the sensory and sympathetic aspects of familial dysautonomia.

Child psychiatric problems in "autonomous dysfunction".

The Riley-Day syndrome, also known by the name Familial Dysautonomia, is characterized by a marked deficit in autonomic homeostatic function. A review of the literature and a case illustration describe the physical, emotional, social and learning problems. It is new known that sub-normal intelligence is not part of the syndrome. The impact of the symptoms on the child and on the mother-child relationship may aggravate the deficient emotional balance. Since marked improvement of the condition does occur, especially in patients who reach the age of six, a hopeful attitude in the guidance and treatment is justified and highly beneficial.

Personality development and familial dysautonomia.

The study sought to establish baselines for personality and frequency of psychopathology in familial dysautonomia (FD). Fifty FD patients, aged 6 to 28 years, served as subjects. FD subjects in all age ranges manifest neurotic patterns, but show no greater incidence of more severe pathology than is found in the general population. the arrested psychologic development seen in FD is described, together with the phenomenon of periodic lapses in judgment. The organic impairment of cognitive functions is discussed. Recommendations for treatment are proposed.

A sensory-integrative approach to familial dysautonomia.

Familial dysautonomia, a relatively rare hereditary condition, consists of a baffling array of nervous system malfunctions that seriously disturb the lives of the young victims and their families. Since several of the deficits can be identified as sensory-integrative and as such have been successfully treated in other contexts, it is suggested that sensory integration therapy may benefit these children. Results of a ten-month-old Isralei child appear to support this conjecture and suggest further exploration of the sensory integration approach in evaluation and treatment of dysautonomia and related conditions.

Intellectual development and familial dysautonomia.

The study examined adaptive trends in cognitive development among individuals with familial dysautonomia and sought to establish new base rates of intelligence for the dysautonomic population. Fifty-two subjects, aged 6 to 28 years, were administered the Wechsler scales of intelligence. The results indicate that there is less cognitive impairment than previous research would suggest, and that more dysautonomic children are capable of adjusting to standard school programs than was heretofore thought possible. Specific deficits seen in this population are discussed along with a rationale for deleting the term retarded where most of these individuals are concerned.