Janice C Wong1, Kailey Walsh2, Douglas Hayden3,4, Florian S Eichler5,6. 1. Department of Neurology, University of California San Francisco, San Francisco, CA, USA. 2. Department of Neurology, Massachusetts General Hospital, 55 Fruit Street, ACC 708, Boston, MA, 02114, USA. 3. Harvard Medical School, Boston, MA, USA. 4. Biostatistics Center, Massachusetts General Hospital, Boston, MA, USA. 5. Department of Neurology, Massachusetts General Hospital, 55 Fruit Street, ACC 708, Boston, MA, 02114, USA. feichler@partners.org. 6. Harvard Medical School, Boston, MA, USA. feichler@partners.org.
Abstract
OBJECTIVES: Cerebrotendinous xanthomatosis (CTX) is a rare inherited neurodegenerative disorder in bile acid synthesis. The natural history of neurological abnormalities in CTX is not well understood. The object of this study was to determine neurological progression in CTX. METHODS: A literature search on PubMed for "cerebrotendinous xanthomatosis" yielded 91 publications that reported cases of CTX patients. Two independent reviewers abstracted information about the presence and age of onset of neurological abnormalities in published CTX cases. For each neurological abnormality, we estimated the probability of its onset at any given age using cumulative incidence function analysis. We also present our own case series, in which five CTX patients were evaluated. RESULTS: The literature search yielded 194 CTX cases (ages ranging from newborn to 67 years old). The most common neurological abnormalities were corticospinal tract abnormalities including weakness, hyperreflexia, spasticity, Babinski sign (59.8%), ataxia (58.8%), cognitive decline (46.4%), and gait difficulty (38.1%); 68 (35.0%) had baseline cognitive problems. Cumulative incidence function analysis revealed that ataxia, gait difficulties, and corticospinal tract abnormalities developed throughout life, while cognitive decline tended to develop later in life. Of the less common neurological abnormalities, seizures, psychiatric changes and speech changes developed throughout life, while parkinsonism and sensory changes tended to develop later in life. Our case series corroborated this temporal pattern of neurological abnormalities. CONCLUSION: We provide estimates for the neurological progression of CTX, categorizing neurological abnormalities according to time and probability of development. Our approach may be applicable to other rare disorders.
OBJECTIVES:Cerebrotendinous xanthomatosis (CTX) is a rare inherited neurodegenerative disorder in bile acid synthesis. The natural history of neurological abnormalities in CTX is not well understood. The object of this study was to determine neurological progression in CTX. METHODS: A literature search on PubMed for "cerebrotendinous xanthomatosis" yielded 91 publications that reported cases of CTXpatients. Two independent reviewers abstracted information about the presence and age of onset of neurological abnormalities in published CTX cases. For each neurological abnormality, we estimated the probability of its onset at any given age using cumulative incidence function analysis. We also present our own case series, in which five CTXpatients were evaluated. RESULTS: The literature search yielded 194 CTX cases (ages ranging from newborn to 67 years old). The most common neurological abnormalities were corticospinal tract abnormalities including weakness, hyperreflexia, spasticity, Babinski sign (59.8%), ataxia (58.8%), cognitive decline (46.4%), and gait difficulty (38.1%); 68 (35.0%) had baseline cognitive problems. Cumulative incidence function analysis revealed that ataxia, gait difficulties, and corticospinal tract abnormalities developed throughout life, while cognitive decline tended to develop later in life. Of the less common neurological abnormalities, seizures, psychiatric changes and speech changes developed throughout life, while parkinsonism and sensory changes tended to develop later in life. Our case series corroborated this temporal pattern of neurological abnormalities. CONCLUSION: We provide estimates for the neurological progression of CTX, categorizing neurological abnormalities according to time and probability of development. Our approach may be applicable to other rare disorders.
Authors: Andrea Mignarri; Maria Teresa Dotti; Marina Del Puppo; Gian Nicola Gallus; Antonio Giorgio; Alfonso Cerase; Lucia Monti Journal: Neuroradiology Date: 2012-03-15 Impact factor: 2.804
Authors: Luis F Gonzalez-Cuyar; Brian Hunter; Peggy L R Harris; George Perry; Mark A Smith; Rudy J Castellani Journal: Redox Rep Date: 2007 Impact factor: 4.412
Authors: David A Price Evans; Kawther A Salah; Mashael A Mobrad; William D Mitchell; Maria Olin; Gosta Eggertsen Journal: Saudi Med J Date: 2007-07 Impact factor: 1.484
Authors: Mohamed Ahmed Ghassem; Aziza Mounach; Julien H Djossou; Hamza Toufik; Najlae El Ouardi; Lahsen Achemlal; Ahmed Bezza Journal: Case Rep Rheumatol Date: 2021-05-20
Authors: Marie Beaudin; Antoni Matilla-Dueñas; Bing-Weng Soong; Jose Luiz Pedroso; Orlando G Barsottini; Hiroshi Mitoma; Shoji Tsuji; Jeremy D Schmahmann; Mario Manto; Guy A Rouleau; Christopher Klein; Nicolas Dupre Journal: Cerebellum Date: 2019-12 Impact factor: 3.847