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Tuberculous Meningitis (TBM) is the most common form of central nervous system Tuberculosis (TB), accounting for 5-6% of extrapulmonary TB cases. Nowadays, TBM continues to be a major topic in public health because of its high prevalence worldwide. This retrospective study aimed to describe the clinical, laboratory, and imaging characteristics at admission; and in-hospital outcome of adult Mexican patients with TBM. We collected data from medical records of patients aged ≥18 years diagnosed with TBM according to the uniform case definition for clinical research who were treated at Tijuana General Hospital between January 2015 and March 2018 and compared them according to the subtype of diagnosis. We included 41 cases (26 males, median age 28 years, range 18-57 years), 13 (31.7%) patients were HIV positive, and 21 (51.2%) were illicit drug users. At admission, 7 (17.1%) patients were in stage I, 22 (53.6%) in stage II, and 12 (29.3%) in stage III. A definitive diagnosis was established in 23 (56.1%) patients, probable in 14 (34.1%), and possible in four (9.8%). Molecular testing was positive in 83% of the cases, yielding significantly higher positive results than other microbiological studies. There were eight (19.5%) deaths, without statistical difference between mortality and not having a definitive diagnosis (p = 0.109). We found that the baseline characteristics of our population were similar to those described by other authors worldwide. In this series, molecular testing showed to be very useful when used in the early stages, particularly in subjects with subacute onset of headache, fever, weight loss, and altered mental status.

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Hereditary transthyretin-mediated (hATTR) amyloidosis is a progressive, debilitating disease often resulting in early-onset, life-impacting autonomic dysfunction. The effect of the RNAi therapeutic, patisiran, on autonomic neuropathy manifestations in patients with hATTR amyloidosis with polyneuropathy in the phase III APOLLO study is reported. Patients received patisiran 0.3 mg/kg intravenously (n = 148) or placebo (n = 77) once every 3 weeks for 18 months. Patisiran halted or reversed polyneuropathy and improved quality of life from baseline in the majority of patients. At baseline, patients in APOLLO had notable autonomic impairment, as demonstrated by the Composite Autonomic Symptom Score-31 (COMPASS-31) questionnaire and Norfolk Quality of Life-Diabetic Neuropathy (Norfolk QOL-DN) questionnaire autonomic neuropathy domain. At 18 months, patisiran improved autonomic neuropathy symptoms compared with placebo [COMPASS-31, least squares (LS) mean difference, - 7.5; 95% CI: - 11.9, - 3.2; Norfolk QOL-DN autonomic neuropathy domain, LS mean difference, - 1.1; - 1.8, - 0.5], nutritional status (modified body mass index, LS mean difference, 115.7; - 82.4, 149.0), and vasomotor function (postural blood pressure, LS mean difference, - 0.3; - 0.5, - 0.1). Patisiran treatment also led to improvement from baseline at 18 months for COMPASS-31 (LS mean change from baseline, - 5.3; 95% CI: - 7.9, - 2.7) and individual domains, orthostatic intolerance (- 4.6; - 6.3, - 2.9) and gastrointestinal symptoms (- 0.8; - 1.5, - 0.2). Rapid worsening of all study measures was observed with placebo, while patisiran treatment resulted in stable or improved scores compared with baseline. Patisiran demonstrates benefit across a range of burdensome autonomic neuropathy manifestations that deteriorate rapidly without early and continued treatment.

INTRODUCTION:Autonomic dysfunction, an early symptom of transthyretin amyloidosis (ATTR amyloidosis), requires investigations not readily available in many clinics. Although monitoring of orthostatic hypotension (OH) will not be a substitute for more specialized tests, it can add important information about initiation of dysautonomia. The aim of this study was to investigate whether simple blood pressure (BP) monitoring may be a useful tool for evaluation of disease progression and an early sign of autonomic dysfunction. METHODS:BP and OH data were from subjects enrolled in the Transthyretin Amyloidosis Outcomes Survey (THAOS). Characteristics associated with changes in BP and orthostatic difference were identified by regression analyses. RESULTS:OH tended to be present relatively early in the course of disease and was more common at enrollment (11.7%) than either diarrhea (2.4%) or unintentional weight loss (3.1%). In subjects with OH at enrollment, progressive increase in systolic and diastolic orthostatic difference was observed. OH was also associated with significantly worse quality of life. DISCUSSION:BP variability is a useful tool for assessing disease onset and severity in ATTR amyloidosis, particularly in patients with OH. Trial registration ClinicalTrials.gov: NCT00628745.