Outcomes of de-prescribing proton pump inhibitors during acute admissions in a general medical unit: a pilot study.

The study describes the feasibility and short-to-medium-term efficacy of an evidence-based proton pump inhibitor (PPI) de-prescribing initiative undertaken as part of routine clinical care during acute admissions in a general medical unit. Of the 44 (median (IQR) age 75.5 (13.75) years; females 25 (57%)) who participated in the study, de-prescription was maintained in 29 (66%) and 27 (61%) patients at 12 and 26 weeks respectively.

Prevalence and predictors of inappropriate dosing of direct oral anticoagulants.

BACKGROUND: Information on inappropriate dosing of direct oral anticoagulants (DOACs) is scarce in the Australian context. AIM: To describe the prevalence and potential predictors of inappropriate dosing of DOACs. METHODS: Patients who received DOACs during admission under a general medical unit over a 2-year period (from January 2017 to December 2018) were retrospectively studied. Appropriateness of the dosing regimen was verified against the recommendations of the Therapeutic Goods Administration of Australia. Data were obtained from medical records and analysed in univariate and multivariate logistic regression models. The variables associated with under- and overdosing were also determined. RESULTS: A total of 203 (mean age 71.6 ± 14.5 years, females 52%) patients were studied. Inappropriate dosing occurred in 44 (22%) patients: underdosing 27 (13%) and overdosing 17 (8%). Age ≥75 years (P < 0.01), lower estimated creatinine clearance (CrCl) (P < 0.01), prescription of DOAC prior to index admission (P < 0.01) and higher Charlson Comorbidity Index (P < 0.01), HAS-BLED (P < 0.01) and CHA2 DS2 -VASc (P < 0.01) scores had a significant univariate association with inappropriate dosing. However, in the multivariate logistic regression only lower CrCl (odds ratio (OR) 1.04, 95% confidence interval (CI): 1.01-1.07, P < 0.01) and prescription of DOAC prior to index admission (OR 2.62, 95% CI: 1.01-6.75, P = 0.047) remained significantly associated with inappropriate dosing. Impaired renal function also had a significant association with underdosing (OR 1.04, 95% CI: 1.01-1.07, P = 0.01) and borderline significance with overdosing (OR 1.03, 95% CI: 1.00-1.07, P = 0.06). CONCLUSION: Inappropriate dosing of DOACs, especially underdosing, is common in clinical practice. Clinicians should exercise due diligence when prescribing DOACs to patients with renal impairment and in outpatient settings.

Diagnosis and Management of Supine and Nocturnal Hypertension in Orthostatic Hypotension: A Review.

The prevalence of supine and nocturnal hypertension (S-N-HT) is high among patients with orthostatic hypotension (OH), especially in those who have a neurogenic aetiology. The evidence suggests that S-N-HT exacerbates OH, although it is unclear whether pharmacologic treatment of S-N-HT will improve OH. S-N-HT has also been associated with target organ damage. Therefore, assessment and management of S-N-HT should be an integral part of managing OH, but it is often overlooked in clinical practice.

Normocalcaemic primary hyperparathyroidism: is nephrolithiasis more common than osteoporosis?

BACKGROUND: Normocalcaemic primary hyperparathyroidism (NPHPT) is often under-recognised in clinical practice. AIM: To determine the prevalence and clinical significance of NPHPT in an unselected sample in an acute hospital setting. METHODS: Patients aged >18 years who had measurement of an elevated serum parathyroid hormone (PTH ≥ 7 pmol/L) during 12 months from 1 January 2017 to 31 December 2017 were retrospectively studied. NPHPT was defined by the presence of elevated serum PTH with normal albumin-corrected serum calcium on two or more occasions after excluding secondary causes. Patients were followed up for 2 years. Relevant data were collected by review of electronic medical records. RESULTS: Of the 2593 patients who had PTH measured during the study period, 1278 had serum PTH ≥ 7 pmol/L. Hypercalcaemic primary hyperparathyroidism (PHPT) was diagnosed in 174 patients. Secondary causes for elevated serum PTH were identified in 993 patients: 815 (chronic kidney disease - estimated glomerular filtration rate < 60 mL/min/1.73 m2 or renal transplant), 98 (vitamin D deficiency - 25(OH)D < 50 nmol/L), 28 (gastric bypass surgery), 38 (medications), 13 (malabsorption or post-thyroidectomy) and 1 (hypercalciuria). Data were incomplete for 80 patients. The prevalence of NPHPT with and without the exclusion of hypercalciuria was 0.19% (5) and 0.39% (10) respectively. The prevalence of nephrolithiasis in NPHPT was higher than PHPT (100% vs 15% among five patients (P < 0.001) and 50% vs 15% among 10 patients (P = 0.014)). The prevalence of osteoporosis was not significantly different between NPHPT and PHPT (20% vs 45% among five patients (P = 0.389) and 30% vs 45% among 10 patients (P = 0.518)). CONCLUSION: These findings give further credence to the diagnosis of NPHPT as a clinical entity. Nephrolithiasis may be a greater problem than osteoporosis in NPHPT compared with PHPT. This needs prospective evaluation.

Predictors of bleeding in patients receiving direct oral anticoagulants.

BACKGROUND: The predictors of clinically significant bleeding events (CSBE) associated with direct oral anticoagulants (DOAC) are poorly characterised in the literature. AIM: To determine the incidence and predictors of CSBE in patients receiving DOAC. METHODS: Patients who received DOAC during admission to a general medical unit over a 2-year period were retrospectively studied. Following the index admission, patients were followed for 12 months or for the duration of treatment (if the latter was less than 12 months). The relevant data were obtained by review of medical records. RESULTS: A total of 203 patients was studied over a mean follow-up period of 293 (±81) days. The incidence of CSBE was 13.7 (95% confidence interval (CI): 9.5-21.1) per 100 person-years. Age ≥ 75 years (P = 0.01), concurrent use of antiplatelet medications (P = 0.02) and lower estimated creatinine clearance (CrCl) (P = 0.03) had a significant univariate association with CSBE. However, in the multivariate logistic regression, only concurrent use of antiplatelet medications remained significantly associated with CSBE (adjusted odds ratio (OR) 3.6; 95% CI: 1.4-9.6; P = 0.01). Concurrent use of antiplatelet medications was also independently associated with major bleeding events (MBE) (adjusted OR 4.9; 95% CI: 1.1-21.4; P = 0.04). Although 39 (19.2%) patients received antiplatelet medications, the indications for concurrent antiplatelet use complied with current guidelines in only 3 (7.7%) patients. CONCLUSION: Caution should be exercised when prescribing antiplatelet medications with DOAC as this combination is a potential risk factor for both major and non-major clinically significant bleeding events. In most patients, the concurrent use of antiplatelet medications was discordant with the current consensus guidelines.

Masked Hypertension: A Systematic Review.

BACKGROUND: Masked phenomenon, Masked Hypertension (MHT) and Masked Uncontrolled Hypertension (MUCH) is a well-defined clinical entity. However, many aspects of MHT/MUCH remain unclear. METHODS: We systematically reviewed the published literature on MHT/MUCH from 1 January 2000 to 31 June 2018 with a particular focus on epidemiology, clinical significance, evaluation and management. Meta-analyses were performed with respect to prevalence, clinical significance and diagnostic agreement between home blood pressure (HBP) and ambulatory BP (ABP) measurements. RESULTS: The overall weighted-mean prevalence of masked phenomenon was 11% [9,14]; MHT 10% [9,11]; and MUCH 13% [8,17]. The weighted-mean prevalence when expressed as a proportion of patients with normal office BP was 32% [25,40]; MHT 28% [15,41]; and MUCH 43% [29,57]. The prevalence of masked phenomenon determined by ABP (11% [8,14]) and HBP (13% [9,16]), was similar. However, ABP appeared to have a greater sensitivity, i.e. proportion of patients diagnosed as having MHT/MUCH was greater with ABP than with HBP (22% v 16%, p<0.05), when both methodologies were applied to the same cohort of patients. The prevalence of MHT was influenced by ethnicities and comorbidities, and in case of MUCH by anti-hypertensive treatment. MHT/MUCH was associated with increased risk of fatal and non-fatal cardiac/cerebrovascular events (relative risk [RR] 2.09 [1.80, 2.44]), and the risk was comparable to sustained hypertension (SHT) (RR 2.26 [1.84, 2.78]). The increased risk occurred regardless of the method of out of office BP assessment; the relative risks for ABP and HBP were 2.38 [1.90, 2.98] and 1.90 [1.57, 2.29] respectively. The diagnostic agreement between ABP and HBP was only modest, kappa = 0.46 [0.40, 0.52], even though the percentage agreement was 83%. The evidence for the management of MHT was scant. CONCLUSIONS: MHT/MUCH is a common BP phenotype with a risk profile similar to that of SHT. Therefore, high risk patients should undergo out of office BP assessment, probably both by HBP and ABP, to confirm diagnosis and be considered for treatment.

The Role of Older Age in Normocytic Anaemia in Type 2 Diabetes Mellitus.

BACKGROUND: Older age has a significant association with anaemia. However, this has not been adequately investigated in the context of specific comorbidities such as Type 2 Diabetes Mellitus (T2DM). OBJECTIVES: To investigate the role of age in Normocytic Anaemia (NCA) and the adverse outcomes of NCA in T2DM. METHODS: Patients with NCA, either unexplained or related to Chronic Kidney Disease (CKD), were recruited from a diabetic clinic over six months. Anaemia was defined as a haemoglobin(Hb) < 130g/l for men and <120g/l for women. The relevant data were obtained by interviewing patients and review of medical records. Patients were followed for 12 months for pre-defined adverse outcomes. RESULTS: Of the 354 patients assessed, 203 were included (mean age 63.12 ± 13.62 years, males 49.8%). The prevalence of NCA was 24% (49). Older age had a significant univariate association with NCA (p < 0.001) and this remained significant (adjusted Odds Ratio (OR) 1.24, 95% CI 1.16- 5.29) after adjusting for estimated Glomerular Filtration Rate (eGFR) < 60ml/min/1.73m2, albuminuria and other potential confounders. Adjusting for eGFR as a continuous variable also confirmed this significant association (OR1.15, 95% CI 1.10-7.01). In the subgroup of patients aged ≥ 75 years, only older age was significantly associated with NCA. The incidence of all-cause mortality and composite cardiovascular/cerebrovascular events was similar in the anaemic and nonanaemic groups. CONCLUSION: NCA is common in T2DM and has a significant association with older age independent of CKD. The anaemia is mild in most patients and appears to have a benign course.

Ambulatory Blood Pressure Monitoring in Type 2 Diabetes Mellitus: A Cross-sectional Study.

BACKGROUND: Ambulatory blood pressure (ABP) monitoring in type 2 diabetes (T2DM) is not yet routine in clinical practice. OBJECTIVES: To quantify abnormal ABP patterns and their associations with diabetic complications, and to assess the reliability of office blood pressure (OBP) for assessing BP in T2DM. METHODS: In a cross-sectional study, eligible patients with T2DM underwent OBP and 24- hour ABP measurements under standardized conditions and screening for diabetic complications. RESULTS: 56 patients (mean age 67 ± 10 years, males 50%) completed assessment. 43(73%) had a known history of hypertension. Non-dipping and nocturnal systolic hypertension (SHT) were prevalent in 31(55%) and 32(57%) patients, respectively. 16(29%) demonstrated masked phenomenon, but only three (7%) demonstrated white coat effect. Nocturnal SHT had a significant association with composite microvascular complications independent of daytime systolic BP control (adjusted odds ratio (OR) 1.72(CI 1.41-4.25). There was no association between other abnormal ABP patterns and diabetic complications. The sensitivity and specificity of OBP for diagnosing HT or assessing BP control was 59% and 68% respectively. The positive and negative predictive values were 74% and 52% respectively. CONCLUSION: Non-dipping, reverse dipping, nocturnal SHT and masked phenomenon are highly prevalent in patients with T2DM with or without a known history of hypertension. Compared with non-dipping, nocturnal SHT may be a stronger predictor of end organ damage. The reliability of OBP for assessing BP in T2DM is only modest. Patients with T2DM are likely to benefit from routine ABP monitoring.

Enablers and barriers to the use of antibiotic guidelines in the assessment and treatment of community-acquired pneumonia-A qualitative study of clinicians' perspectives.

BACKGROUND: Community-acquired pneumonia (CAP) is a common condition and a number of guidelines have been developed for its assessment and treatment. Adherence to guidelines by clinicians varies and particularly the prescribing of antibiotics often remains suboptimal. OBJECTIVE: The aim of this study was to elucidate potential barriers and enablers to the adherence to antibiotic guidelines by clinicians treating CAP in an Australian hospital. METHODS: Semi-structured interviews were conducted with purposively recruited senior prescribers who regularly treat CAP in an Australian hospital. Thematic analysis identified a number of themes and subthemes related to their knowledge, attitudes and behaviours associated with the use of CAP guidelines. RESULTS: Thematic saturation was reached after 10 in-depth interviews. Although similar barriers to the use of guidelines as previously described in the literature were confirmed, a number of novel, potential enablers were drawn from the interviews. Clinicians' acceptance and accessibility of guidelines emerged as enabling factors. Generally positive attitudes towards antimicrobial stewardship services invite leveraging what was described as the relationship-based and hierarchical nature of medical practice to provide personalised feedback and updates to clinicians. CONCLUSIONS: Adding a social and personalised approach of antimicrobial stewardship to policy- and systems-based strategies may lead to incremental improvements in guideline adherent practice when assessing and treating CAP.

Orthostatic hypotension: pathophysiology, assessment, treatment and the paradox of supine hypertension.

Both hypertension and orthostatic hypotension (OH) are strongly age-associated and are common management problems in older people. However, unlike hypertension, management of OH has unique challenges with few well-established treatments. Not infrequently, they both coexist, further compounding the management. This review provides comprehensive information on OH, including pathophysiology, diagnostic workup and treatment, with a view to provide a practical guide to its management. Special references are made to patients with supine hypertension and postprandial hypotension and older hypertensive patients.

Chronic idiopathic normocytic anaemia in older people: the risk factors and the role of age-associated renal impairment.

OBJECTIVES: To characterise the risk factors for chronic idiopathic normocytic anaemia (CINA) in older people, particularly the role of age-associated renal impairment. METHODS: Patients aged ≥65 years admitted to a medical unit over 12 months were assessed. Those with secondary causes of anaemia including chronic kidney disease (CKD) were excluded. CINA was defined as a haemoglobin <130 g/l for men and <120 g/l for women for at least 6 months without any apparent cause. Renal function was determined by estimating creatinine clearance (CrCl) using Cockcroft-Gault formula, and glomerular filtration rate (GFR) using modification of diet in renal disease (MDRD) and chronic kidney disease epidemiology collaboration (CKD-EPI) formulas. RESULTS: 116 had CINA. Controls were 572. The mean estimates of renal function were significantly lower in cases as compared with controls (P < 0.001). The risk of CINA increased by 12.6, 10.4 and 12 %, respectively, for each unit decrease in CrCl, MDRD-eGFR and CKD-EPI-eGFR, independent of age and other covariates. The adjusted odds ratios for CINA in those with CrCl, MDRD or CKD-EPI eGFR <60 ml/min/1.73 m2 were 2.68 (CI 1.53-4.70); 2.70 (CI 1.57-4.62) and 2.12 (CI 1.46-3.74), respectively. Other covariates in the model that were independently associated with CINA included advanced age, diabetes mellitus (DM), use of angiotensin converting enzyme inhibitor (ACEI) or angiotensin receptor blocker (ARB), history of dementia and living in a residential care facility. CONCLUSIONS: Age-associated renal impairment independently contributes to CINA. Other potential risk factors for CINA include advanced age, DM and ACEI or ARB use.

In-hospital Falls in Older Patients: The Risk Factors and The Role of Hyponatraemia.

BACKGROUND: Hyponatraemia has been associated with increased falls risk. However, this has not been adequately investigated in the context of In-Hospital Falls (IHFs). OBJECTIVES: To determine the potential risk factors for IHFs, particularly the role of hyponatraemia. METHODS: Patients aged >65 years with an incident IHF during admissions under a General Internal Medicine (GIM) Unit over six months were studied. For each case, two age and sex matched controls were randomly selected from patients who were admitted under the GIM unit during the same time as the cases. The relevant data were obtained by review of medical records. RESULTS: The prevalence of IHF was 7.2%. Hyponatraemia had a significant univariate association with IHF (P=0.005). This association remained significant even after controlling the covariates (adjusted odds ratio (OR) 1.890, 95% confidence interval (CI) 1.391-3.497, P=0.021). The frequency of IHF did not vary with the severity of hyponatraemia (P=0.267). The other variables that had an independent association with IHFs were admission falls (OR 1.570, CI 1.340-5.833, P=0.030), use of psychotropic medications (OR=4.440, CI 2.051-13.240, P<0.001) and diuretics (OR=0.827, CI 0.767-0.901, P=0.010), and cardiovascular diagnosis (OR=0.916, CI 0.893-0.942, P=0.039). CONCLUSION: Hyponatraemia has an independent association with increased risk of IHFs. Other potential risk factors for IHFs include admission falls and psychotropic medication use. Diuretic use and cardiovascular diagnosis have a significant inverse association with IHFs.

The clinical utility of ambulatory blood pressure monitoring (ABPM): a review.

The current evidence suggests that ambulatory blood pressure monitoring (ABPM) should be an integral part of the diagnosis and management of hypertension. However, its uptake in routine clinical practice has been variable. This paper reviews the current evidence for the role of ABPM in clinical practice, including in hypotensive disorders and in specific comorbidities. It further discusses the clinical significance of abnormal ambulatory blood pressure patterns and hypertensive syndromes such as white coat, masked and resistant hypertension.

Hip fracture risk factors and the discriminability of hip fracture risk vary by age: a case-control study.

AIMS: To determine the important risk factors for hip fracture and the discriminability of hip fracture risk in different age cohorts (≤80 years, >80 years). METHODS: Consecutive admissions of hip fracture over 24 months in those aged >60 years, and an age- and sex-matched control derived from admissions under a medical unit were prospectively assessed. The risk factors and the discriminabilty of hip fracture risk by age were investigated for each sex in univariate and multivariate models. The area under the curve (AUC) statistics from the receiver operating characteristic curve analysis was used to estimate the ability of the independent risk factors to discriminate hip fracture risk. RESULTS: The important risk factors in women aged ≤80 years were lower bodyweight, previous osteoporotic fracture, hip fracture in first-degree relatives and lower plasma 25OHD, and their discriminative effect was (AUC) 0.69. Previous osteoporotic fracture and lower plasma 25OHD were the important risk factors in men aged ≤80 years, with a discriminative effect of 0.83. In the >80-year age cohorts, only falls was independently associated with hip fracture in both sexes, with discriminative effects of 0.60 and 0.62 in females and males, respectively. CONCLUSIONS: The overall discrimination of hip fracture risk appears less adequate in those aged >80 years when compared with those aged ≤80 years. Although skeletal factors have a greater risk association with hip fracture in patients aged ≤80 years, it is falls that is important in those aged >80 years. The relative importance of risk factors also appears to vary between the sexes in those aged ≤80 years.

The prevalence of Neurally Mediated Syncope in older patients presenting with unexplained falls.

AIMS: To determine the prevalence and clinical significance of carotid sinus syndrome (CSS) and vasovagal syncope (VVS), the two common types of Neurally Mediated Syncope (NMS), in a cohort of older patients with unexplained falls. METHODS: Patients presenting with unexplained and accidental falls were identified from 200 consecutive admissions of falls in patients aged 65 years and older admitted to the Rapid Assessment Medical Unit (RAMU) in a teaching hospital. A sample of unexplained and accidental fallers underwent carotid sinus massage (CSM) and tilt table testing (TTT) as per a standardised protocol. Baseline characteristics, clinical variables and the prevalence of NMS were compared between the two groups. RESULTS: Falls were unexplained in 26% of patients. The prevalence of NMS was 24% (5/21) among patients with unexplained falls who underwent assessment for NMS, whereas it was nil (0/17) in patients with accidental falls (P=0.050). The prevalence of previous falls was significantly higher in patients with unexplained falls (P=0.0025), but all other baseline characteristics were similar between the two groups. CONCLUSION: Falls are unexplained in a significant number of older patients presenting to acute hospitals. The assessment of unexplained fallers for NMS is clinically important as this may be aetiologically related in nearly a quarter of these patients.

Efficacy and safety of oral continuous low-dose versus short-term high-dose vitamin D: a prospective randomised trial conducted in a clinical setting.

OBJECTIVE: To compare the efficacy and safety of a 10-day, high-dose v a 3-month, continuous low-dose oral cholecalciferol course in a vitamin D deficient population. The primary end points were the change in serum 25-hydroxyvitamin D (25(OH)D) concentrations at 3 months and the development of hypercalcaemia and hypercalciuria. DESIGN, SETTING AND PARTICIPANTS: Fifty-nine vitamin D deficient inpatients (serum 25(OH)D < or = 50 nmol/L) were enrolled in a prospective, randomised, open-label trial. Participants were randomly assigned to a high-dose regimen of cholecalciferol 50 000 IU daily for 10 days or a 3-month, continuous low-dose cholecalciferol regimen of 3000 IU daily for 30 days, followed by 1000 IU daily for 60 days. Both groups received calcium citrate 500 mg daily. RESULTS: Twenty-six patients completed the study within 3 - or + 1 months. The mean increases in serum 25(OH)D were similar in both the high- and low-dose groups (to 55 v 51 nmol/L, respectively; P = 0.9). There was no significant difference in the proportion of subjects who attained serum 25(OH)D concentrations > 50 nmol/L between the high- and low-dose groups (9/10 v 13/14, respectively; P = 1.0). Hypercalciuria (urine calcium > 7.5 mmol/day) occurred in three patients (two low-dose, one high-dose), while renal impairment worsened in one patient. No patient developed hypercalcaemia (corrected calcium > 2.6 mmol/L), vitamin D toxicity (25(OH)D > 200 nmol/L) or nephrolithiasis during the study. CONCLUSION: Both the 10-day, high-dose and the 3-month, low-dose cholecalciferol regimens effectively increased serum 25(OH)D to within the normal range. The high-dose regimen may be an effective and cheap alternative for patients with vitamin D deficiency. TRIAL REGISTRATION: Australian Clinical Trials Registry ACTRN 12607000338460.

Pitfalls in managing falls.

Falls are common in the elderly and one of the most common reasons for older people to seek medical help. To illustrate the diagnostic dilemmas of this common clinical problem, we present a case study of a woman with a history of recurrent falls.

Osteoporotic fractures and vitamin D deficiency.

CASE STUDY: A caucasian woman aged 79 years, with a history of hypertension, hyperlipidaemia, and osteoarthritis, was referred for assessment of osteoporosis and generalised musculoskeletal pain after surgery for a right midshaft femoral fracture. Further history revealed she had suffered nonspecific musculoskeletal pain, particularly of the pelvic girdle, and unsteady gait for many weeks, but denied suffering any falls. She had limited mobility due to osteoarthritis of both knees. She had been mostly housebound and was on an animal product restricted diet in view of her history of hypercholesterolaemia. Initial X-rays confirmed an incomplete fracture of the midshaft of the right femur. She had an orthopaedic review, and subsequent bone scan and X-rays (Figure 1) revealed incomplete fractures of the midshaft of both femurs and the seventh rib. She was managed conservatively (alendronate 70 mg per week) and progress was closely monitored. Three weeks later, she presented to the emergency department with worsening right thigh pain and difficulty in weightbearing. X-rays revealed an extension of the right femoral fracture traversing the entire cortex that required surgery. Physical examination revealed a mild thoracic kyphosis. There was no muscle or bone tenderness, proximal muscle weakness, or other significant abnormality. The plasma biochemistry revealed: mild hypocalcaemia (1.98 mmol/L), hypophoshataemia (0.7 mmol/L), raised alkaline phosphatase (ALP) (216 iu/L), low 25-hydroxyvitamin D (250HD) (22 nmol/L), and a mildly raised parathyroid hormone (PTH) level (8 pmol/L). Thyroid, renal, and liver functions were normal. The patient was treated with nine capsules of Ostelin 1000 per day, which was tapered over 8 weeks to one capsule. The repeat plasma 25OHD after 6 weeks was 56 nmol/L, and her musculoskeletal symptoms were completely resolved. There was normalisation of biochemical abnormalities and X-rays demonstrated healing of both femoral fractures. A bone biopsy taken at the time of surgery revealed an increased amount of osteoid. However, undecalcified bone sections were not examined, nor was quantitative histomorphometry performed. Dual energy X-ray absortiometry (DEXA) scan revealed a T-score of -3.32 at the hip and -1.38 at the lumbar spine. Corresponding Z-scores were -1.05 and -0.7.

A case of intravascular lymphomatosis (IVL) presenting as polyneuropathy.

Intravascular lymphomatosis (IVL) is a rare, yet important, cause of a variety of unexplained neurological syndromes. In this clinical context, the only clue to the diagnosis may be a significantly raised plasma lactate dehydrogenase (LDH) on a background of clinical features of a systemic illness.