BackgroundNeurosarcoidosis is a rare variant of sarcoidosis and is only described in small cohort studies. We define clinical features, treatment and outcome of patients with neurosarcoidosis over the last 35 years.MethodsWe performed a systematic review and meta-analysis of studies on neurosarcoidosis published between 1980 and 2016. Studies were included if they reported at least 5 cases. Studies describing one specific neurological presentation were excluded.ResultsWe identified 29 articles describing 1088 patients diagnosed between 1965 and 2015. Neurosarcoidosis occurred in 5% of patients with systemic sarcoidosis. Mean age at presentation was 43 years and neurological symptoms were the first clinical manifestation of sarcoidosis in 52%. The most commonly reported feature of neurosarcoidosis was cranial neuropathy in 55%, with the facial and optic nerve most commonly affected, followed by headache in 32%. Pleiocytosis and elevated CSF protein were found in 58 and 63%. MRI of the brain showed abnormalities in 70%. Chest X-ray, chest CT, or gallium-67-scintigraphy showed findings consistent with sarcoidosis in 60%, 70% and 69%, respectively. First line therapy with corticosteroids was initiated in 434 of 539 patients (81%). Second and third line therapy was started in 27 and 9%. Outcome consisted of complete remission in 27%, incomplete remission in 32%, stable disease in 24%, deterioration in 6% and death in 5%.ConclusionNeurosarcoidosis has a heterogeneous clinical presentation and the diagnosis can be difficult because of low sensitivity of ancillary investigations. New treatments have emerged, but nevertheless one third of patients do not respond to treatment. Prospective cohort studies and RCTs on treatment are urgently needed.Electronic supplementary materialThe online version of this article (doi:10.1186/s12883-016-0741-x) contains supplementary material, which is available to authorized users.

Autosomal recessive distal renal tubular acidosis (rdRTA) is characterised by severe hyperchloraemic metabolic acidosis in childhood, hypokalaemia, decreased urinary calcium solubility, and impaired bone physiology and growth. Two types of rdRTA have been differentiated by the presence or absence of sensorineural hearing loss, but appear otherwise clinically similar. Recently, we identified mutations in genes encoding two different subunits of the renal α-intercalated cell's apical H + -ATPase that cause rdRTA. Defects in the B1 subunit gene ATP6V1B1, and the a4 subunit gene ATP6V0A4, cause rdRTA with deafness and with preserved hearing, respectively. We have investigated 26 new rdRTA kindreds, of which 23 are consanguineous. Linkage analysis of seven novel SNPs and five polymorphic markers in, and tightly linked to, ATP6V1B1 and ATP6V0A4 suggested that four families do not link to either locus, providing strong evidence for additional genetic heterogeneity. In ATP6V1B1, one novel and five previously reported mutations were found in 10 kindreds. In 12 ATP6V0A4 kindreds, seven of 10 mutations were novel. A further nine novel ATP6V0A4 mutations were found in "sporadic" cases. The previously reported association between ATP6V1B1 defects and severe hearing loss in childhood was maintained. However, several patients with ATP6V0A4 mutations have developed hearing loss, usually in young adulthood. We show here that ATP6V0A4 is expressed within the human inner ear. These findings provide further evidence for genetic heterogeneity in rdRTA, extend the spectrum of disease causing mutations in ATP6V1B1 and ATP6V0A4, and show ATP6V0A4 expression within the cochlea for the first time.A cid-base regulation by the kidney is tightly controlled through the coupled processes of acid secretion and bicarbonate reabsorption via intercalated cells of the nephron's collecting duct segment. The result is regulated secretion into the urine of the net acid load provided by the human diet. The main proton pump responsible for urinary acidification by α-intercalated cells, the apical H + -ATPase, is a multi-subunit structure with a "head and stalk" configuration. The V 1 (head) and V 0 (membrane anchored) domains are responsible for ATP hydrolysis and transmembrane proton translocation respectively.

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