Combined treatment with LDL-apheresis, chenodeoxycholic acid and HMG-CoA reductase inhibitor for cerebrotendinous xanthomatosis

Ito, Shingo; Kuwabara, Satoshi; Sakakibara, Ryuji; Oki, Takeshi; Hiroshi, Arai; Oda, Shinya; Hattori, Takamichi

doi:10.1016/j.jns.2003.07.005

Cited by 30 publications

(11 citation statements)

References 12 publications

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“…24 Recent studies suggest that the combined treatment of chenodeoxycholic acid and hydroxymethyl-glutaryl-coenzimeA (HMG-CoA) reductase inhibitors is a rational approach. 25 Thus, we treated our patient with chenodeoxycholic acid (300 mg per day) and simvastatin (20 mg per day), but we did not observe an obvious improvement of the neurological symptoms. We postulate that the treatment is only effective if initiated at the fi rst sign of symptoms (cataracts, diarrhea, and mild neurologic abnormalities) because once xanthomas appear, it is usually too late to obtain satisfactory results.…”

Section: Discussionmentioning

confidence: 76%

Bilateral Achilles Tendon Enlargement

Miao¹,

Yang²,

Tao³

2011

Orthopedics

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Cerebrotendinous xanthomatosis is a rare, autosomal-recessive, lipid-storage disease with accumulation of cholestanol in most tissues, particularly within the Achilles tendons. It has been characterized both clinically and biochemically, and recently from the molecular biological aspect as well. Juvenile cataract, childhood diarrhea, mental retardation, cerebellar ataxia, and tendon xanthomas are the most prominent features of this disease. Bilateral symmetrical firm masses of Achilles tendons may be the first symptom the patient recognizes because it can jeopardize his or her ability to walk. However, the treatment strategies for tendon tumors vary. In a recent case, we diagnosed the disease properly, according to the clinical manifestations and the radiological and laboratory examinations. The genetic mutation was characterized by analyzing sterol 27-hydroxylase from the patient's family (located on nucleotide 599) and led to a nonsense mutation. It is a unique type of mutation that has never been reported to our knowledge. Tendon lesions are characterized by the loss of muscle fibers and accumulation of lipid products. To help the patient regain the strength of the Achilles tendon and walking abilities, a large area of tendon tumor was excised, followed by reconstruction with a tibialis posterior allograft, which is the second strongest tendon in the foot and ankle. Although the use of this type of graft is uncommon, the final result was satisfactory. At the 10-month follow-up examination, the patient could walk easily without pain. This case report suggests that the surgical procedure will provide an alternative for the repair of large-area degenerative Achilles tendons.

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Section: Discussionmentioning

confidence: 76%

Bilateral Achilles Tendon Enlargement

Miao¹,

Yang²,

Tao³

2011

Orthopedics

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“…If the treatment is started early in the disease some symptoms, like ataxia, can be stopped or reversed (Class III) . Cerebrotendinous xanthomatosis (CTX): Chenodeoxycholic acid, which normalizes bile acid synthesis and suppresses the cholestanol biosynthesis, stabilizes clinical signs of neuropathy in a dosage of 750 mg/day . HMG‐CoA reductase inhibitors are also effective in improving clinical signs by reducing the cholestanol concentration (two Class III studies), but caution is required because they may induce muscle damage and in some cases even rhabdomyolysis . Niemann−Pick type C: Miglustat is a small amino sugar molecule that inhibits glycosphingolipid (GSL) synthesis. It reduces GSL accumulation in the brain and improves some clinical symptoms, like dysphagia, but the current data in terms of significant functional benefit are not too convincing yet.…”

Section: Management Of Chronic Cerebellar Ataxiasmentioning

confidence: 99%

“…Cerebrotendinous xanthomatosis (CTX): Chenodeoxycholic acid, which normalizes bile acid synthesis and suppresses the cholestanol biosynthesis, stabilizes clinical signs of neuropathy in a dosage of 750 mg/day [63]. HMG-CoA reductase inhibitors are also effective in improving clinical signs by reducing the cholestanol concentration (two Class III studies), but caution is required because they may induce muscle damage and in some cases even rhabdomyolysis [64,65]. NiemannÀPick type C: Miglustat is a small amino sugar molecule that inhibits glycosphingolipid (GSL) synthesis.…”

Section: Drug Treatmentmentioning

confidence: 99%

EFNS/ENS Consensus on the diagnosis and management of chronic ataxias in adulthood

Warrenburg

Gaalen

Boesch

et al. 2014

Euro J of Neurology

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Background and objectives The ataxias are a challenging group of neurological diseases due the aetiological heterogeneity and the complexity of the genetic subtypes. This guideline focuses on the heredodegenerative ataxias. The aim is to provide a peer‐reviewed evidence‐based guideline for clinical neurologists and other specialist physicians responsible for the care of patients with ataxia. Methods This guideline is based on systematic evaluations of the relevant literature and on three consensus meetings of the task force. Diagnosis If acquired causes are ruled out, and if the disease course is rather slowly progressive, a (heredo)degenerative disease is likely. A positive family history gives much guidance. In the case of a dominant family history, first line genetic screening is recommended for spinocerebellar ataxia (SCA) 1, 2, 3, 6, 7 and 17 (level B), and in Asian patients also for dentatorubral‐pallidoluysian atrophy (DRPLA). In the case of recessive disease, a stepwise diagnostic work‐up is recommended, including both biochemical markers and targeted genetic testing, particularly aimed at Friedreich's ataxia, ataxia telangiectasia, ataxia due to vitamin E deficiency, polymerase gamma gene (POLG gene, various mutations), autosomal recessive spastic ataxia of Charlevoix−Saguenay (ARSACS) and ataxia with oculomotor apraxia (AOA) types 1 and 2. If family history is negative, we still advise to screen for the more common dominant and recessive ataxias. In addition, if onset is below 45 years we recommend the full work‐up for recessive ataxias; if onset is above 45 years we recommend to screen for fragile X mental retardation 1 FMR1 premutations (good practice points). In sporadic cases with an onset after 30 years, a diagnosis of multiple system atrophy should be considered (good practice point). In particular the genetic work‐up will change over the upcoming years due to the diagnostic utility of new techniques such as gene panel diagnostics based on next generation sequencing for routine work‐up, or even whole exome and genome sequencing for selected cases. Treatment Some of the rare recessive ataxias are treatable, but for most of the heredodegenerative ataxias treatment is purely symptomatic. Idebenone is not effective in Friedreich's ataxia (level A). Riluzole (level B) and amantadine (level C) might provide symptomatic relief, irrespective of exact etiology. Also, varenicline for SCA3 patients (level B) can be considered. There is level Class II evidence to recommend physiotherapy, and Class III data to support occupational therapy.

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“…75 Nevertheless, because FXR induces CYP3A4 expression 57 and because most of the statins are metabolized by CYP3A4, safety issues should be carefully monitored for this combination. It must also be noted that reported improvements of the lipid profile were not translated into gain in brain functions 146,147 and that the levels of various lipid parameters (cholestanol, lathosterol) remained supraphysiological during treatment. 75 Therefore, it could be of interest to study the influence of more potent FXR agonists than CDCA, like 6-ECDCA (Table 2).…”

Section: Treating Cerebrotendinous Xanthomatosis and Inborn Errors Inmentioning

confidence: 99%

The Farnesoid X Receptor

Claudel

Staels

Kuipers

2005

ATVB

439

106

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Key Words: bile acid Ⅲ FXR Ⅲ glucose metabolism Ⅲ lipid Ⅲ nuclear receptor A s a direct consequence of the obesity epidemic, 1-3 the prevalence of the metabolic syndrome is increasing at an alarming rate. 4 Almost 25% of the adult US population is currently affected, and the situation is even worse in people older than 60 years. 5 The metabolic syndrome has been defined by the National Cholesterol Education Program as a cluster of at least 3 of 5 criteria: insulin resistance and glucose intolerance, abdominal obesity, hypertension, low high-density lipoprotein (HDL) cholesterol, and hypertriglyceridemia. 6 Given the fact that the metabolic perturbation associated with the metabolic syndrome predisposes to cardiovascular diseases and stroke, 7 novel and more specific therapeutical strategies are urgently needed. Certain ligand-activated nuclear receptors provide promising new targets for this purpose. In this review, we discuss the biology of the Farnesoid X receptor (FXR, NRIH4), recently identified as a modulator of lipid and glucose homeostasis.Nuclear receptors are transcription factors that, on ligand binding by specific molecules and cofactor recruitment, regulate the expression of specific target genes. 8 FXR is highly expressed in liver and intestine 9 and was cloned during a search for new Retinoid X receptor (RXR or NR2B1) heterodimers. 9,10 Originally described as a farnesol-activated receptor interacting with RXR, and accordingly named, FXR was later identified as a Original

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Combined treatment with LDL-apheresis, chenodeoxycholic acid and HMG-CoA reductase inhibitor for cerebrotendinous xanthomatosis

Cited by 30 publications

References 12 publications

Bilateral Achilles Tendon Enlargement

Bilateral Achilles Tendon Enlargement

EFNS/ENS Consensus on the diagnosis and management of chronic ataxias in adulthood

The Farnesoid X Receptor

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