Sensory neuropathy as a manifestation of multiple acyl-coenzyme A dehydrogenase deficiency.

Multiple acyl-coenzyme A dehydrogenase deficiency (MADD) is a rare metabolic disorder which typically manifests with muscle weakness. However, despite late-onset MADD being treatable, it is often misdiagnosed, due in part to the heterogeneity of presentations. We report a case of late-onset MADD manifesting first as a sensory neuropathy before progressing to myopathic symptoms and acute metabolic decompensation. Early diagnostic workup with acylcarnitine profiling and organic acid analysis was critical in patient outcome; metabolic decompensation and myopathic symptoms were completely reversed with riboflavin supplementation and dietary modification, although sensory neuropathy persisted. Clinical consideration of MADD as part of the differential diagnosis of neuropathy with myopathy is crucial for a timely diagnosis and treatment of MADD.

The MS Remyelinating Drug Bexarotene (an RXR Agonist) Promotes Induction of Human Tregs and Suppresses Th17 Differentiation In Vitro.

The retinoid X receptor agonist bexarotene promotes remyelination in patients with multiple sclerosis. Murine studies have also demonstrated that RXR agonists have anti-inflammatory effects by enhancing the ability of all-trans-retinoic acid (atRA) to promote T-regulatory cell (Treg) induction and reduce Th17 differentiation in vitro. By stimulating human naïve CD4 T-cells in the presence of Treg or Th17 skewing cytokines, we show that bexarotene also tips the human Treg/Th17 axis in favor of Treg induction, but unlike murine cells this occurs independently of atRA and retinoic acid receptor signaling. Tregs induced in the presence of bexarotene express canonical markers of T-regulation and are functionally suppressive in vitro. Circulating Treg numbers did not increase in the blood of trial patients receiving bexarotene; we believe this is because Treg induction is likely to occur within tissues. These findings lend support to developing RXR agonists as treatments of autoimmune diseases, in particular multiple sclerosis.

Hydrocephalus as the first presenting symptom of neurosarcoidosis in two patients: a diagnosis more forthcoming in the context of systemic disease.

Sarcoidosis is a multisystem disorder, characterised histologically by the presence of non-caseating epithelioid granulomas with exclusion of other granulomatous diseases. While the lungs and lymph nodes are affected in 90%, approximately 5% of patients have neurological involvement. The clinical manifestations of neurosarcoidosis (NS) are diverse, making diagnosis especially difficult in patients without known systemic disease. Hydrocephalus occurs in only 9% of patients with NS and although uncommon, is an important manifestation because it is associated with high morbidity and mortality. We report two cases of NS presenting with hydrocephalus, one as the first presentation of sarcoidosis and one in a patient with known multisystem sarcoidosis. The patient without systemic sarcoidosis posed the greater diagnostic challenge and followed a protracted course with multiple surgical interventions, progression of central nervous system inflammation and significant physical disability.

Herpes zoster oticus with meningitis masquerading as malignant otitis externa.

This is a case of an 85-year-old woman whom was admitted with otalgia and an abducens nerve palsy alongside a Pseudomonas otitis externa; she was presumed to have malignant otitis externa. However, despite optimum treatment and resolution of her otitis externa, she went on to develop an ipsilateral facial nerve palsy and sensorineural hearing loss. After further investigation, it was discovered that varicella-zoster meningitis was causing her polyneuropathy. She eventually responded to antivirals and steroids and, at follow-up, her sixth and seventh cranial nerve palsies had completely resolved, though a hearing deficit remained. This case highlights the importance of keeping a diagnosis under review, with the help of the multidisciplinary team, when the clinical course is not progressing as expected.

Using saccades to diagnose covert hepatic encephalopathy.

Covert Hepatic Encephalopathy (CHE), previously known as Minimal Hepatic Encephalopathy, is a subtle cognitive defect found in 30-70 % of cirrhosis patients. It has been linked to poor quality of life, impaired fitness to drive, and increased mortality: treatment is possible. Despite its clinical significance, diagnosis relies on psychometric tests that have proved unsuitable for use in a clinical setting. We investigated whether measurement of saccadic latency distributions might be a viable alternative. We collected data on 35 cirrhosis patients at Addenbrooke's Hospital, Cambridge, with no evidence of clinically overt encephalopathy, and 36 age-matched healthy controls. Performance on standard psychometric tests was evaluated to determine those patients with CHE as defined by the World Congress of Gastroenterology. We then compared visually-evoked saccades between those with CHE and those without, as well as reviewing blood test results and correlating saccadic latencies with biochemical parameters and prognostic scores. Cirrhosis patients have significantly longer median saccadic latencies than healthy controls. Those with CHE had significantly prolonged saccadic latencies when compared with those without CHE. Analysis of a cirrhosis patient's saccades can diagnose CHE with a sensitivity of 75 % and a specificity of 75 %. We concluded that analysis of a cirrhosis patient's saccadic latency distributions is a fast and objective measure that can be used as a diagnostic tool for CHE. This improved early diagnosis could direct avoidance of high-risk activities such as driving, and better inform treatment strategies.