Dysautonomia Foundation

Familial dysautonomia (FD) is an autosomal recessive hereditary sensory and autonomic neuropathy (HSAN, type 3) expressed at birth with profound sensory loss and early death. The FD founder mutation in the ELP1 gene arose within the Ashkenazi Jews in the sixteenth century and is present in 1:30 Jews of European ancestry. The mutation yield a tissue-specific skipping of exon 20 and a loss of function of the elongator-1 protein (ELP1), which is essential for the development and survival of neurons. Patients with FD produce variable amounts of ELP1 in different tissues, with the brain producing mostly mutant transcripts. Patients have excessive blood pressure variability due to the failure of the IXth and Xth cranial nerves to carry baroreceptor signals. Neurogenic dysphagia causes frequent aspiration leading to chronic pulmonary disease. Characteristic hyperadrenergic "autonomic crises" consisting of brisk episodes of severe hypertension, tachycardia, skin blotching, retching, and vomiting occur in all patients. Progressive features of the disease include retinal nerve fiber loss and blindness, and proprioceptive ataxia with severe gait impairment. Chemoreflex failure may explain the high frequency of sudden death in sleep. Although 99.5% of patients are homozygous for the founder mutation, phenotypic severity varies, suggesting that modifier genes impact expression. Medical management is currently symptomatic and preventive. Disease-modifying therapies are close to clinical testing. Endpoints to measure efficacy have been developed, and the ELP1 levels are a good surrogate endpoint for target engagement. Early intervention may be critical for treatment to be successful.

Hereditary sensory and autonomic neuropathy type III (HSAN III), also known as familial dysautonomia or Riley–Day syndrome, results from an autosomal recessive genetic mutation that causes a selective loss of specific sensory neurones, leading to greatly elevated pain and temperature thresholds, poor proprioception, marked ataxia and disturbances in blood pressure control. Stretch reflexes are absent throughout the body, which can be explained by the absence of functional muscle spindle afferents – assessed by intraneural microelectrodes inserted into peripheral nerves in the upper and lower limbs. This also explains the greatly compromised proprioception at the knee joint, as assessed by passive joint‐angle matching. Moreover, there is a tight correlation between loss of proprioceptive acuity at the knee and the severity of gait impairment. Surprisingly, proprioception is normal at the elbow, suggesting that participants are relying more on sensory cues from the overlying skin; microelectrode recordings have shown that myelinated tactile afferents in the upper and lower limbs appear to be normal. Nevertheless, the lack of muscle spindles does affect sensorimotor control in the upper limb: in addition to poor performance in the finger‐to‐nose test, manual performance in the Purdue pegboard task is much worse than in age‐matched healthy controls. Unlike those rare individuals with large‐fibre sensory neuropathy, in which both muscle spindle and cutaneous afferents are absent, those with HSAN III present as a means of assessing sensorimotor control following the selective loss of muscle spindle afferents.

To evaluate the relationship between postural orthostatic tachycardia syndrome (POTS) and pregnancy. Cross-sectional survey. International. A total of 8941 female patients with a diagnosis of POTS. Data from the survey were analysed using descriptive measures and stratified for comparisons. Symptom course of POTS during pregnancy. Secondary outcomes included pregnancy loss, POTS onset during pregnancy and the impacts of a comorbid diagnosis of Ehlers-Danlos syndrome or an autoimmune disorder on symptoms during pregnancy. Overall, 40.8% (n=3652) of participants reported one or more pregnancies. Most participants experienced worsening of symptoms in the first (62.6%) and third (58.9%) trimesters and 3months after pregnancy (58.7%), and 81.1% experienced worsening symptoms at any point in their pregnancy. Most participants with worsening symptoms in the first trimester also experienced worsening symptoms in the second (61.6%) and third (68.1%) trimesters, but if they improved in the first trimester then this improvement persisted in the second and third trimesters. Of participants who reported that POTS was triggered by a specific event (41.3%), 8.1% reported pregnancy as the trigger for the onset. Postural orthostatic tachycardia syndrome symptoms in the first trimester of pregnancy may help predict symptom course throughout the duration of pregnancy. Some individuals may experience an initial onset of POTS during pregnancy. This novel information may guide clinicians in counselling patients with POTS who are planning pregnancy.

In the current consensus diagnostic criteria, the diagnosis of probable multiple system atrophy (MSA) is based solely on clinical findings, whereas neuroimaging findings are listed as aid for the diagnosis of possible MSA. There are overlapping phenotypes between MSA-parkinsonian type and Parkinson's disease, progressive supranuclear palsy, and dementia with Lewy bodies, and between MSA-cerebellar type and sporadic adult-onset ataxia resulting in a significant diagnostic delay and misdiagnosis of MSA during life. In light of an ongoing effort to revise the current consensus criteria for MSA, the Movement Disorders Society Multiple System Atrophy Study Group performed a systematic review of original articles published before August 2019. We included articles that studied at least 10 patients with MSA as well as participants with another disorder or control group for comparison purposes. MSA was defined by neuropathological confirmation, or as clinically probable, or clinically probable plus possible according to consensus diagnostic criteria. We discuss the pitfalls and benefits of each diagnostic test and provide specific recommendations on how to evaluate patients in whom MSA is suspected. This systematic review of relevant studies indicates that imaging and autonomic function tests significantly contribute to increasing the accuracy of a diagnosis of MSA.

Penjangkitan wabah Avian influenza menjadi persoalan kesehatan yang menimbulkan dampak serius di bidang yang lain, seperti ekonomi, sosial-budaya, politik, pertahanan, dan keamanan, baik di tingkat nasional maupun internasional, termasuk di Indonesia. Berbagai upaya telah dilakukan untuk mengantisipasi penyebaran wabah ini, salah satunya dengan tindakan karantina untuk menghambat penyakit tersebut dengan tetap mempertimbangkan kelancaran perjalanan, yang dilakukan di area pintu masuk, antara lain di bandar udara, pelabuhan laut, stasiun angkutan darat, sebagai tempat perbatasan antara suatu wilayah dan wilayah luar. Karena itu, tujuan penelitian ini adalah untuk mengetahui peran karantina sebagai alat pencegah untuk menghalangi penjangkitan Avian influenza dan efektivitas implementasinya di Bandara Internasional Soekarho-Hatta. Penelitian ini menggunakan metode deskriptif kualitatif. Lokasi penelitian ini adalah Kantor Kesehatan Pelabuhan (KKP) Kelas I Jakarta Bandara Soekarno Hatta. Data yang digunakan adalah data primer yang diperoleh melalui observasi dan wawancara dan data sekunder yang diperoleh lewat studi dokumenter. Data yang terkumpul dianalisis dengan teknik deskriptif kualitatif. Hasil penelitian ini menunjukkan bahwa di Indonesia, kegiatan karantina diterapkan terutama di Kantor Kesehatan Pelabuhan Kelas I Jakarta dengan tugas dan fungsi pokok mencegah masuknya penyakit karantina dan penyakit menular berpotensi wabah. Sementara itu, di Kantor Kesehatan Pelabuhan Kelas I Bandara Soekarno-Hatta, tugas dan fungsi pokoknya adalah melaksanakan karantina pada pintu masuk wilayah negara Republik Indonesia. Pelaksanaan tugas dan fungsi itu dipengaruhi oleh beberapa faktor antara lain: dasar legalitas (landasan hukum dan operasional) organisasi, sarana dan prasarana, sumber daya manusia, Standar Operasional Prosedur, Kerjasama Lintas-Sektor dalam penerapan teknologi informasi serta dukungan dana untuk pembiayaan operasional kegiatan. Efektivitas berbagai upaya tersebut sangat diperlukan untuk mendukung kokohnya ketahanan nasional dalam upaya penyempurnaan kegiatan karantina yang dilaksanakan KKP Kelas I Bandara Soekarno-Hatta. Pertama, revisi UU No. 2/1962 tentang Karantina perlu dilakukan agar lebih disesuaikan dengan Peraturan Kesehatan Internasional 2005. Kedua, pembenahan sarana dan prasarana perlu dilakukan untuk mendukung pelaksanaan pengawasan higienitas dan sanitasi pesawat sebagai alat angkut, pelayanan kesehatan berupa perbaikan sarana observasi penderita, laboratorium maupun kegiatan rujukan penderita. Ketiga, pengembangan sumber daya manusia, rekrutmen tenaga operasional sesuai dengan tugas melalui pendidikan dan pelatihan. Keempat, penyempurnaan Standar Operasional Prosedur, yang sesuai dengan karakteristik penyakit, dengan tetap mempertimbangkan kelancaran pelaku perjalanan. Kelima, mempermantap kerjasama lintas-sektor antar- dan inter-lembaga serta jaringan informasi pihak banda dan di luar negeri. Dan keenam, mengoptimalkan ketersediaan dana dalam upaya mendukung kegiatan karantina dengan menggali sumber dana dari pihak yang terkait. The outbreak of Avian influenza epidemics is a health problem resulting in serious impact in economic, socio-cultural, political, defence and security sectors at the national and international levels, including in Indonesia. Various efforts are done to anticipate the epidemic, one of which is to do the quarantine efforts of impeding its dissemination while considering smooth traveling in gateways, such as in airport, seaport and land transport station as main borders between territory and the outside. Therefore, purpose of this study is to find out the role of quarantine as the preventive instrument of inhibiting the outbreak of Avian influenza and its effectiveness of implementation in Soekarno-Hatta International Airport. The study used a descriptive qualitative method. The location of the study was the Airport Health Office of Class I Jakarta. Data used were both primary data obtained from interview and secondary data obtained through documentary study. Data collected were then analyzed by a descriptive qualitative technique. Result of the study indicates that the quarantine efforts in Indonesia were particularly done in Airport Health Officer of Class I (AHO-I) Jakarta with main task and function of inhibiting the dissemination of quarantined diseases and potential infectious disease epidemics. In AHO-I of Soekarno-Hatta International Airport, the main task and function was to do quarantine activity in gateways of the Republic of Indonesia. The performance of main tasks and functions were influenced by several factors, such as regulation, infrastructure, human resource, Standard Operating Procedures, cross-sector cooperation in the application of information technology, and fund to support operational finance. The effectiveness of various efforts is highly required to support the national security of completing the quarantine programs in AHO-I of Soekarno-Hatta International Airport. First, revision of Act No. 2/1962 on Quarantine should be done in order to be adapted to International Health Regulation of 2005. Second, the improvement of infrastructures is necessary to do for supporting the performance of hygienist and sanitation monitoring of plane as transport facility, health services by improving patient observation facility, laboratory, and patient reference guides. Third, human resource development and operational personnel recruitment appropriate with main tasks by education and training. Four, completing the Standard Operating Procedures adapted to the characteristics of disease while considering smooth traveling. Five, the establishment of intra- and inter-institutional cross-sector cooperation and the information networks of domestic and foreign airports. And six, optimizing fund sufficiency in the efforts of supporting the quarantine activity by exploring the source of fund from related parties.

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BackgroundPutaminal diffusivity in brain magnetic resonance diffusion-weighted imaging (DWI) is increased in patients with the parkinsonian variant of multiple system atrophy (MSA-P) compared to Parkinson disease (PD) patients.PurposeWe performed a systematic review and meta-analysis to evaluate the diagnostic accuracy of DWI to distinguish MSA-P from PD.MethodsStudies on DWI were identified through a systematic PubMed and Clarivate Analytics® Web of Science® Core Collection search. Papers were selected based on stringent inclusion criteria; minimum requirement was the inclusion of MSA-P and PD patients and documented true positive, true negative, false positive and false negative rates or overall sample size and reported sensitivity and specificity. Meta-analysis was performed using the hierarchical summary receiver operating characteristics curve approach.ResultsThe database search yielded 1678 results of which 9 studies were deemed relevant. Diagnostic accuracy of putaminal diffusivity measurements were reported in all of these 9 studies, whereas results of other regions of interest were only reported irregularly. Therefore, a meta-analysis could only be performed for putaminal diffusivity measurements: 127 patients with MSA-P, 262 patients with PD and 70 healthy controls were included in the quantitative synthesis. The meta-analysis showed an overall sensitivity of 90% (95% confidence interval (CI): 76.7%-95.8%) and an overall specificity of 93% (95% CI: 80.0%-97.7%) to distinguish MSA-P from PD based on putaminal diffusivity.ConclusionPutaminal diffusivity yields high sensitivity and specificity to distinguish clinically diagnosed patients with MSA-P from PD. The confidence intervals indicate substantial variability. Further multicenter studies with harmonized protocols are warranted particularly in early disease stages when clinical diagnosis is less certain.

The maintenance of blood pressure in the upright position requires intact autonomic cardiovascular reflexes. Diseases that affect the sympathetic innervation of the cardiovascular system result in a sustained fall in blood pressure upon standing (i.e., neurogenic orthostatic hypotension) that can impair the blood supply to the brain and other organs and cause considerable morbidity and mortality. Here we review treatment options for neurogenic orthostatic hypotension and include an algorithm for its management that emphasizes the importance of non-pharmacologic measures and provides guidance on pharmacologic treatment options.