Leriglitazone halts disease progression in adult patients with early cerebral adrenoleukodystrophy.

Cerebral adrenoleukodystrophy (CALD) is an X-linked rapidly progressive demyelinating disease leading to death usually within a few years. The standard of care is hematopoietic stem cell transplantation (HSCT), but many men are not eligible due to age, absence of a matched donor, or lesions of the corticospinal tracts (CST). Based on the ADVANCE study showing that leriglitazone decreases the occurrence of CALD, we treated 13 adult CALD patients (19-67 years of age) either not eligible to HSCT (n= 8) or awaiting HSCT (n= 5). Patients were monitored every 3 months with standardized neurological scores, plasma biomarkers and brain MRI comprising lesion volumetrics and diffusion tensor imaging. The disease stabilized clinically and radiologically in 10 patients with up to 2 years of follow-up. Five patients presented with gadolinium enhancing CST lesions that all turned gadolinium negative and, remarkably, regressed in four patients. Plasma neurofilament light chain levels stabilized in all 10 patients and correlated with lesion load. The two patients who continued to deteriorate were over 60 years of age with prominent cognitive impairment. One patient rapidly died from Covid19. These results suggest that leriglitazone can arrest disease progression in adults with early-stage CALD and may be an alternative treatment to HSCT.

Urodynamic analysis in multiple system atrophy: characterisation of detrusor-sphincter dyssynergia.

In multiple system atrophy (MSA), parkinsonism and a cerebellar syndrome are associated with autonomic dysfunction. Both bladder neck dysfunction and external sphincter denervation have been implicated in detrusor-sphincter dyssynergia. However, urethral dysfunction may not be adequately reflected by a single global measurement of urethral pressure. Pressure assessment at several levels of the urethra is needed to unravel the mechanisms of bladder-urethra dysfunction. Here, we evaluated the use of multiple sensor pressure transducers to assess bladder-sphincter function in 52 patients with MSA in comparison to patients with Parkinson's disease (PD) who were matched for age and severity in the "off" condition. Urinary dysfunction appeared significantly earlier in MSA (<2 years) than in PD (>5 years). Detrusor under-activity with dysuria was observed in 58% of MSA patients within 4 years and in 76% of patients thereafter. Detrusor-urethral dyssynergia in MSA patients was always better characterized by multiple sensor pressure transducer measurement of bladder and urethral pressure than by a single global measurement. This new approach may prove useful for differential diagnosis of parkinsonian syndromes, and especially MSA.

Usefulness of nasal provocation tests in occupational rhinitis.

OBJECTIVE: The aim of the study was to determine whether Nasal Provocation Tests (NPT) could help in the diagnosis of occupational rhinitis (OR). METHODS: Changes in nasal airway resistance (NAR), measured by posterior rhinomanometry during specific nasal challenge associated with per and post test clinical scores, were compared to a prior probability, based on the patient's history, determined by occupational physicians, in 41 hairdressers and 33 bakers referred for suspected OR. RESULTS: A DeltaNAR >or= 150% defined the positivity of the NPT. DeltaNAR demonstrated 50% sensitivity and a 86% specificity in hairdressers and a 95% sensitivity with 100 % specificity in bakers. DeltaNAR presented significant positive correlations with both per (p = 0.0003, r = 0.48) and post test clinical scores (p < 0.005, r = 0.39). The addition of clinical scores increased the sensitivity to 100% in hairdressers with 81% specificity. CONCLUSIONS: The NPT constitutes a safe procedure of nasal reactivity with good levels of sensitivity and specificity in both hairdressers and bakers when nasal resistance and clinical scores are taken into account.

Thyrotoxic periodic paralysis in Caucasian patients: a diagnostic challenge.

Secondary hypokalemic periodic paralysis is rare. However, when it occurs, it is usually associated with Graves' disease and it is mostly diagnosed in Asiatic male patients. In this report, we analyze the diagnostic procedure in three cases of hypokalemic periodic paralysis associated with Graves' disease, diagnosed in three different emergency care units over the last 3 years. Three Caucasian men (26, 30, and 39 years of age) came to the emergency care unit for acute tetraparesia. One of them had suffered 15 stereotypical episodes of tetraparesia during the last 2 years. Goiter was present in each case. Kalemia was 1.8, 2.1, and 3 mmol/l, respectively. Triggering events such as considerable sugar intake and physical exercise were present in two cases. In all cases, low TSH levels, high FT4 levels, and anti-TSH receptor antibodies led to the diagnosis of Graves' disease. All patients were treated with potassium supplementation and neomercazole. Outcome was good with a follow-up of 6, 9, and 24 months, respectively. Emergency care practitioners should be aware of this diagnosis, which may affect Caucasian patients presenting with transient tetraparesia in a primary care unit.