Cerebrotendinous xanthomatosis without neurological involvement.

BACKGROUND: Cerebrotendinous xanthomatosis (CTX) is an autosomal recessively inherited inborn error of metabolism. Neurological symptoms are considered to be a clinical hallmark of untreated adult patients. We describe a 'milder CTX phenotype', without neurological involvement. METHODS: We performed a retrospective patient file study in 79 genetically confirmed Dutch patients with CTX (55 patients aged ≥ 21 years) to study the clinical heterogeneity of CTX. We studied the frequency of adult patients with CTX without neurological involvement at diagnosis, in our Dutch cohort, and included a family from South Africa and patients from Italy, USA, Chile and Asia from the literature. RESULTS: In total, we describe 19 adult patients with CTX from 16 independent families, without neurological symptoms at diagnosis. A relatively small percentage (21%, n = 4) had a history of cataract. The majority, 84% (n = 16), presented with tendon xanthomas as the sole or predominant feature. The majority of patients showed increased plasma cholesterol levels. No correlation was found between this 'milder phenotype', the cholestanol levels and the CYP27A1 genotype. In addition, we describe three novel mutations in the CYP27A1 gene. CONCLUSIONS: This study shows the clinical heterogeneity of CTX, highlighting the existence of a 'milder phenotype', that is without neurological involvement at diagnosis. Adult patients with CTX may present with tendon xanthomas as the sole or predominant feature, mimicking familial hypercholesterolemia. It is important to realize that the absence of neurological symptoms does not rule out the development of future neurological symptoms. As CTX is a treatable disorder, early diagnosis and initiation of treatment when additional clinical signs occur is therefore essential.

Improving neurophysiological biomarkers for functional myoclonic movements.

INTRODUCTION: Differentiating between functional jerks (FJ) and organic myoclonus can be challenging. At present, the only advanced diagnostic biomarker to support FJ is the Bereitschaftspotential (BP). However, its sensitivity is limited and its evaluation subjective. Recently, event related desynchronisation in the broad beta range (13-45 Hz) prior to functional generalised axial (propriospinal) myoclonus was reported as a possible complementary diagnostic marker for FJ. Here we study the value of ERD together with a quantified BP in clinical practice. METHODS: Twenty-nine patients with FJ and 16 patients with cortical myoclonus (CM) were included. Jerk-locked back-averaging for determination of the 'classical' and quantified BP, and time-frequency decomposition for the event related desynchronisation (ERD) were performed. Diagnostic gain, sensitivity and specificity were obtained for individual and combined techniques. RESULTS: We detected a classical BP in 14/29, a quantitative BP in 15/29 and an ERD in 18/29 patients. At group level we demonstrate that ERD in the broad beta band preceding a jerk has significantly higher amplitude in FJ compared to CM (respectively -0.14 ± 0.13 and +0.04 ± 0.09 (p < 0.001)). Adding ERD to the classical BP achieved an additional diagnostic gain of 53%. Furthermore, when combining ERD with quantified and classical BP, an additional diagnostic gain of 71% was achieved without loss of specificity. CONCLUSION: Based on the current findings we propose to the use of combined beta ERD assessment and quantitative BP analyses in patients with a clinical suspicion for all types of FJ with a negative classical BP.

Two patients with a neuroendocrine tumour of the small intestine and paraneoplastic myasthenia gravis.

UNLABELLED: This paper reports on two patients with a long-standing diagnosis of an ENETS stage IV neuroendocrine tumour (NET) of the small intestine who developed neurological symptoms. The first patient only had bulbar symptoms and tested positive for acetylcholine receptor antibodies. The second patient had more classical symptoms of fatigable diplopia and muscle weakness of the legs, but no detectable antibodies. The diagnosis of paraneoplastical myasthenia gravis (MG) was postulated. Both patients were treated with pyridostigmine for MG and octreotide for the NETs. Interestingly, treatment of the NETs resulted in improvement of myasthenic symptoms. Paraneoplastic MG has been described to occur with certain malignancies, mainly thymoma. Herein, we prove that the association with gastrointestinal NETs, however, rare, is also one to be considered by clinicians dealing with either of these diseases. The pathogenesis has yet to be elucidated. LEARNING POINTS: NETs are rare malignancies with a wide variety of symptoms.Paraneoplastic MG can occur with various types of malignancies.Herein, we provide evidence of paraneoplastic MG in association with a grade IV NET of the small intestine.Treatment of the NETs resulted in remission of myasthenic symptoms in one patient.