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Brain Abnormalities Seen in Children with Severe Form of Diabetes

By MedImaging International staff writers
Posted on 06 Aug 2012
Image: Brain scans identified regions of significantly reduced gray matter (right column) and white matter (left column) in young people with Wolfram syndrome. The brainstem and the cerebellum were particularly affected (Photo courtesy of the Washington University School of Medicine in St. Louis).
Image: Brain scans identified regions of significantly reduced gray matter (right column) and white matter (left column) in young people with Wolfram syndrome. The brainstem and the cerebellum were particularly affected (Photo courtesy of the Washington University School of Medicine in St. Louis).
Children with a rare syndrome that includes a form of insulin-dependent diabetes have brain abnormalities that appear to create cognitive problems later in life, according to new imaging research.

The scientists, from Washington University School of Medicine in St. Louis (MO, USA), examined children with Wolfram syndrome, which causes insulin-dependent diabetes in childhood. The disorder also causes hearing and vision loss and kidney difficulties. As patients get older, they can develop cognitive difficulties and dementia, and more than half die before their 30th birthday. Earlier case studies had used imaging to identify brain abnormalities, but doctors had assumed those changes occurred late in the disease process when Wolfram’s patients got older. The new findings suggest, however, that some alterations in the brain occur early in childhood.

The study’s findings were published in the online July 11, 2012, in the journal Public Library of Science (PLoS) One. “This work strongly suggests that brain changes occur very early in the disease,” said first author Tamara Hershey, PhD. “The Wolfram gene is important throughout the body--in the heart, retina, pancreas, and so on. The pancreas is affected very early in development eventually leading to diabetes, so it stands to reason that other organs like the brain may also be affected at an early age, even before a child experiences any cognitive problems.”

Wolfram syndrome results from mutations in a single gene called WSF-1, which was first identified in 1998 by the late M. Alan Permutt, MD, a former professor of medicine and of cell biology and physiology. He later developed an animal model of the disorder. In 2010, Dr. Permutt organized the world’s first clinic exclusively for patients with Wolfram syndrome. The initiative gathered children worldwide to St. Louis for testing and assessment. Another clinic was held in 2011, and a third will take place this summer at St. Louis Children’s Hospital.

Dr. Hershey, a professor of psychiatry, of neurology and of radiology, centered on the neurologic features of Wolfram syndrome. She leads the scientific efforts of the interdisciplinary clinic, along with Bess A. Marshall, MD, associate professor of pediatrics, who is the clinic’s medical director. Almost a dozen Washington University faculty members evaluate patients at the Wolfram clinic as part of studies to better understand the syndrome.

For the new study, Dr. Hershey obtained brain scans of Wolfram patients ages 5-25 and other young patients who only had type 1 diabetes, along with healthy controls in the same age range. The study represents the first time that scientists have attempted to measure and statistically quantify brain differences in patients with Wolfram syndrome. “These individuals are intact cognitively, and some of them are very smart, high-functioning kids,” she noted. “But we have been able to detect significant differences in the size of certain brain structures, leading us to believe that some of these differences must happen during brain development.”

In particular, Dr. Hershey’s group has identified alteration in the brainstem and the cerebellum. They also discovered that the skulls of these children tended to be smaller than would have been expected, based on their ages at the time of the study. The investigators also identified differences in the thickness of the brain’s cortex, in particular, in parts of the cortex related to vision. “We were able to pinpoint those regions of the brain that are most affected in terms of size--the brainstem and the cerebellum,” she stated. “And we also used a type of imaging called diffusion tensor imaging [DTI] that allowed us to measure the integrity of white matter pathways in the brain. Again, we found evidence that the brainstem and the cerebellum white matter were affected in patients with Wolfram syndrome, compared to those with type 1 diabetes only and healthy controls.”

DTI employs magnetic resonance imaging (MRI) to map the brain’s white matter tracts and perform fiber tracking. Wolfram syndrome is very rare, affecting an estimated one in 770,000 children. Before these comprehensive research clinics were established, most of what scientists knew about the brains of patients with the disorder had come from clinical exams of adult patients or autopsies of patients with Wolfram’s.

Dr. Hershey believes that by conducting annual MRI scans and continuing to track patients with Wolfram syndrome over time, it may be possible to distinguish changes that occur during brain development from those that occur due to degeneration related to the disorder.

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Washington University School of Medicine in St. Louis


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86 (38.862228393555): SELECT show_live FROM jos_com_show_setting LIMIT 1
87 (247.95532226562): SELECT fid FROM jos_deeppockets WHERE cat=10 AND id=294741959 AND (type='deeppockets_item' OR type='deeppockets_item_link') AND published='1' LIMIT 1
88 (450.13427734375): SELECT fid FROM jos_deeppockets_archive WHERE cat=10 AND id=294741959 AND (type='deeppockets_item' OR type='deeppockets_item_link') AND published='1' LIMIT 1
89 (638.96179199219): SELECT id,name,title FROM jos_deeppockets WHERE cat=10 AND TYPE='file_folder' AND published=1 AND id != 294743300 AND id != 294743301 AND id != 294743302 AND id != 294743303 AND id != 294743304 AND id != 294743305 AND id != 294743306 AND id != 294743307 AND id != 294743308 AND id != 294743309 AND id != 294743310 AND metakey != 'aacc' ORDER BY `ordering`
90 (658.98895263672): SELECT show_live FROM jos_com_show_setting LIMIT 1
91 (52.928924560547): SELECT show_live FROM jos_com_show_setting LIMIT 1
92 (306.12945556641): SELECT show_live FROM jos_com_show_setting LIMIT 1
93 (46.968460083008): SELECT show_live FROM jos_com_show_setting LIMIT 1
94 (427.9613494873): SELECT show_live FROM jos_com_show_setting LIMIT 1
95 (!!!!! 3124.9523162842): SELECT show_live FROM jos_com_show_setting LIMIT 1
96 (848.05488586426): SELECT show_live FROM jos_com_show_setting LIMIT 1
97 (268.93615722656): SELECT show_live FROM jos_com_show_setting LIMIT 1
98 (900.9838104248): SELECT show_live FROM jos_com_show_setting LIMIT 1
99 (!!!!! 6402.0156860352): SELECT show_live FROM jos_com_show_setting LIMIT 1
100 (540.97175598145): SELECT show_live FROM jos_com_show_setting LIMIT 1
101 (!!!!! 2033.9488983154): SELECT show_live FROM jos_com_show_setting LIMIT 1
102 (!!!!! 8592.8440093994): SELECT show_live FROM jos_com_show_setting LIMIT 1
103 (!!!!! 4467.0104980469): SELECT show_live FROM jos_com_show_setting LIMIT 1
104 (427.0076751709): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294741959 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294741959 AND published='1' LIMIT 1
105 (!!!!! 7103.9199829102): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294741959 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294741959 AND published='1' LIMIT 1
106 (!!!!! 8025.1693725586): SELECT dp.*, ch.title as channel, exp.name as author_name, exp.specialization as author_specialization, exp.images as author_photo FROM jos_deeppockets as dp LEFT JOIN jos_experts as exp ON exp.id = dp.author LEFT JOIN jos_deeppockets as ch ON dp.fid = ch.id WHERE 1=1 AND dp.cat=10 AND dp.id=294741959 AND (dp.type='deeppockets_item' OR dp.type='deeppockets_item_link') AND dp.published='1' LIMIT 1
107 (299.93057250977): SELECT dp.*, ch.title as channel, exp.name as author_name, exp.specialization as author_specialization, exp.images as author_photo FROM jos_deeppockets_archive as dp LEFT JOIN jos_experts as exp ON exp.id = dp.author LEFT JOIN jos_deeppockets as ch ON dp.fid = ch.id WHERE 1=1 AND dp.cat=10 AND dp.id=294741959 AND (dp.type='deeppockets_item' OR dp.type='deeppockets_item_link') AND dp.published='1' LIMIT 1
108 (808.0005645752): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294741959 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294741959 AND published='1' LIMIT 1
109 (!!!!! 7990.837097168): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294741959 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294741959 AND published='1' LIMIT 1
110 (!!!!! 3381.0138702393): SELECT dp.*, ch.title as channel, exp.name as author_name, exp.specialization as author_specialization, exp.images as author_photo FROM jos_deeppockets as dp LEFT JOIN jos_experts as exp ON exp.id = dp.author LEFT JOIN jos_deeppockets as ch ON dp.fid = ch.id WHERE 1=1 AND dp.id=294741959 AND (dp.type='deeppockets_item' OR dp.type='deeppockets_item_link') AND dp.published='1' LIMIT 1
111 (910.04371643066): SELECT dp.*, ch.title as channel, exp.name as author_name, exp.specialization as author_specialization, exp.images as author_photo FROM jos_deeppockets_archive as dp LEFT JOIN jos_experts as exp ON exp.id = dp.author LEFT JOIN jos_deeppockets as ch ON dp.fid = ch.id WHERE 1=1 AND dp.id=294741959 AND (dp.type='deeppockets_item' OR dp.type='deeppockets_item_link') AND dp.published='1' LIMIT 1
112 (614.16625976562): SELECT dp.name, dp.id, dp2.name as channel, ex.name as author_name, ex.specialization, ex.images FROM jos_deeppockets as dp LEFT JOIN jos_experts as ex ON ex.id = dp.author LEFT JOIN jos_deeppockets as dp2 ON dp2.id = dp.fid WHERE dp.author != 0 AND dp.cat = 10 AND dp.published = 1 AND ( (dp.fid = 294743300) OR (dp.fid = 294743301) OR (dp.fid = 294743302) OR (dp.fid = 294743303) OR (dp.fid = 294743304) OR (dp.fid = 294743305) OR (dp.fid = 294743306) OR (dp.fid = 294743307) OR (dp.fid = 294743308) OR (dp.fid = 294743309) OR (dp.fid = 294743310) ) ORDER BY RAND() LIMIT 1
113 (342.84591674805): SELECT dp.name, dp.id, dp2.name as channel, ex.name as author_name, ex.specialization, ex.images FROM jos_deeppockets as dp LEFT JOIN jos_experts as ex ON ex.id = dp.author LEFT JOIN jos_deeppockets as dp2 ON dp2.id = dp.fid WHERE dp.author != 0 AND dp.cat = 10 AND dp.published = 1 AND ( (dp.fid = 294743300) OR (dp.fid = 294743301) OR (dp.fid = 294743302) OR (dp.fid = 294743303) OR (dp.fid = 294743304) OR (dp.fid = 294743305) OR (dp.fid = 294743306) OR (dp.fid = 294743307) OR (dp.fid = 294743308) OR (dp.fid = 294743309) OR (dp.fid = 294743310) ) ORDER BY RAND() LIMIT 1
114 (94.890594482422): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294741959 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294741959 AND published='1' LIMIT 1
115 (61.988830566406): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294741959 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294741959 AND published='1' LIMIT 1
116 (117.06352233887): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294741959 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294741959 AND published='1' LIMIT 1
117 (60.081481933594): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294741959 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294741959 AND published='1' LIMIT 1
118 (77.962875366211): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294741959 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294741959 AND published='1' LIMIT 1
119 (108.00361633301): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294741959 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294741959 AND published='1' LIMIT 1
120 (64.13459777832): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294741959 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294741959 AND published='1' LIMIT 1
121 (56.028366088867): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294741959 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294741959 AND published='1' LIMIT 1
122 (324.01084899902): SELECT * FROM trending_articles WHERE `journal_id` = 10 AND `timestamp` <= NOW() + INTERVAL 7 DAY ORDER BY `order`
123 (!!!!! 54037.094116211): SELECT * FROM jos_deeppockets WHERE jos_deeppockets.cat = 10 AND jos_deeppockets.type = 'deeppockets_item' AND jos_deeppockets.published = 1 AND jos_deeppockets.created + INTERVAL 14 DAY >= NOW() ORDER BY jos_deeppockets.hits DESC LIMIT 7
124 (562.90626525879): SELECT fid FROM jos_deeppockets WHERE cat=10 AND id=294741959 AND type='deeppockets_item' AND published='1' union SELECT fid FROM jos_deeppockets_archive WHERE cat=10 AND id=294741959 AND type='deeppockets_item' AND published='1' LIMIT 1
125 (!!!!! 16130.924224854): ( SELECT dp.id, dp.name, dp.title, dp.video, dp.video_source, dp.created FROM jos_deeppockets AS dp WHERE dp.video != '' AND dp.video_source != '' AND dp.cat = 10 AND dp.published = 1 AND dp.type != 'deeppockets_item_link' ORDER BY created DESC LIMIT 3 ) UNION ( SELECT dpa.id, dpa.name, dpa.title, dpa.video, dpa.video_source, dpa.created FROM jos_deeppockets_archive AS dpa WHERE dpa.video != '' AND dpa.video_source != '' AND dpa.cat = 10 AND dpa.published = 1 AND dpa.type != 'deeppockets_item_link' ORDER BY created DESC LIMIT 3 ) ORDER BY created DESC LIMIT 3
126 (79.154968261719): ( SELECT dp.id, dp.name, dp.title, dp.video, dp.video_source, dp.created FROM jos_deeppockets AS dp WHERE dp.video != '' AND dp.video_source != '' AND dp.cat = 10 AND dp.published = 1 AND dp.type != 'deeppockets_item_link' ORDER BY created DESC LIMIT 3 ) UNION ( SELECT dpa.id, dpa.name, dpa.title, dpa.video, dpa.video_source, dpa.created FROM jos_deeppockets_archive AS dpa WHERE dpa.video != '' AND dpa.video_source != '' AND dpa.cat = 10 AND dpa.published = 1 AND dpa.type != 'deeppockets_item_link' ORDER BY created DESC LIMIT 3 ) ORDER BY created DESC LIMIT 3
127 (298.97689819336): SELECT dp.id, dp.name, dp.title, dp.video, dp.video_source, dp.created FROM jos_deeppockets AS dp WHERE dp.id = 294803337 LIMIT 1
128 (36.001205444336): SELECT dp.id, dp.name, dp.title, dp.video, dp.video_source, dp.created FROM jos_deeppockets AS dp WHERE dp.id = 294803337 LIMIT 1
129 (281.09550476074): SELECT dp.id, dp.name, dp.title, dp.video, dp.video_source, dp.created FROM jos_deeppockets AS dp WHERE dp.id = 294803276 LIMIT 1
130 (46.968460083008): SELECT dp.id, dp.name, dp.title, dp.video, dp.video_source, dp.created FROM jos_deeppockets AS dp WHERE dp.id = 294803276 LIMIT 1
131 (219.10667419434): SELECT dp.id, dp.name, dp.title, dp.video, dp.video_source, dp.created FROM jos_deeppockets_archive AS dp WHERE dp.id = 294803276 LIMIT 1
132 (38.14697265625): SELECT dp.id, dp.name, dp.title, dp.video, dp.video_source, dp.created FROM jos_deeppockets_archive AS dp WHERE dp.id = 294803276 LIMIT 1
133 (247.95532226562): SELECT dp.id, dp.name, dp.title, dp.video, dp.video_source, dp.created FROM jos_deeppockets AS dp WHERE dp.id = 294802958 LIMIT 1
134 (39.100646972656): SELECT dp.id, dp.name, dp.title, dp.video, dp.video_source, dp.created FROM jos_deeppockets AS dp WHERE dp.id = 294802958 LIMIT 1
135 (488.9965057373): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294741959 AND (type='deeppockets_item' OR type='deeppockets_item_link') AND published='1' LIMIT 1
136 (378.84712219238): SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294741959 AND (type='deeppockets_item' OR type='deeppockets_item_link') AND published='1' LIMIT 1
137 (217.91458129883): SELECT name FROM jos_deeppockets WHERE id=212
138 (47.922134399414): SELECT name FROM jos_deeppockets WHERE id=212
139 (653.02848815918): SELECT *, DATE_FORMAT(publish_up,'%d %b %Y') AS date_publish_up, DATE_FORMAT(publish_down,'%d %b %Y') AS date_publish_down FROM jos_events WHERE state=1 AND publish_up > NOW() and extra_info REGEXP '((;)|(^))212((;)|($))' AND catid IN (0,110) ORDER BY publish_up ASC LIMIT 3
140 (567.91305541992): SELECT *, DATE_FORMAT(publish_up,'%d %b %Y') AS date_publish_up, DATE_FORMAT(publish_down,'%d %b %Y') AS date_publish_down FROM jos_events WHERE state=1 AND publish_up > NOW() and extra_info REGEXP '((;)|(^))212((;)|($))' AND catid IN (0,110) ORDER BY publish_up ASC LIMIT 3
141 (98.943710327148): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294741959 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294741959 AND published='1' LIMIT 1
142 (67.949295043945): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294741959 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294741959 AND published='1' LIMIT 1
143 (!!!!! 8911.8480682373): TRUNCATE TABLE jos_trademed_module
144 (191.92695617676): SELECT dp.*, ch.title as channel, exp.name as author_name, exp.specialization as author_specialization, exp.images as author_photo FROM jos_deeppockets as dp LEFT JOIN jos_experts as exp ON exp.id = dp.author LEFT JOIN jos_deeppockets as ch ON dp.fid = ch.id WHERE 1=1 AND dp.cat=10 AND dp.id=294741959 AND (dp.type='deeppockets_item' OR dp.type='deeppockets_item_link') AND dp.published='1' LIMIT 1
145 (716.20941162109): SELECT dp.*, ch.title as channel, exp.name as author_name, exp.specialization as author_specialization, exp.images as author_photo FROM jos_deeppockets_archive as dp LEFT JOIN jos_experts as exp ON exp.id = dp.author LEFT JOIN jos_deeppockets as ch ON dp.fid = ch.id WHERE 1=1 AND dp.cat=10 AND dp.id=294741959 AND (dp.type='deeppockets_item' OR dp.type='deeppockets_item_link') AND dp.published='1' LIMIT 1
146 (494.00329589844): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294741959 AND (type='deeppockets_item' OR type='deeppockets_item_link') AND published='1' LIMIT 1
147 (56.982040405273): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294741959 AND (type='deeppockets_item' OR type='deeppockets_item_link') AND published='1' LIMIT 1
148 (!!!!! 1376.1520385742): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294741959 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294741959 AND published='1' LIMIT 1
149 (92.029571533203): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294741959 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294741959 AND published='1' LIMIT 1
150 (!!!!! 1110.0769042969): SELECT jos_item.* FROM jos_item INNER JOIN jos_number ON jos_item.numberID=jos_number.id WHERE 1=1 AND (jos_item.imgMini<>'') AND jos_item.type='L' AND jos_item.numberID= ( SELECT jos_number.id FROM jos_number WHERE jos_number.journalID IN (10) and jos_number.id in (select distinct jos_number.id from jos_number join jos_item on jos_item.numberid=jos_number.id where jos_item.type='P') ORDER BY (CONVERT(SUBSTRING(issue,1,2),SIGNED) + (CONVERT(SUBSTRING(issue,3,2),SIGNED)*100)) DESC LIMIT 0,1 ) ORDER BY RAND() DESC LIMIT 6
151 (75.101852416992): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294741959 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294741959 AND published='1' LIMIT 1
152 (47.922134399414): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294741959 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294741959 AND published='1' LIMIT 1
153 (425.81558227539): SELECT fid FROM jos_deeppockets WHERE cat=10 AND id=294741959 AND type='deeppockets_item' AND published='1' union SELECT fid FROM jos_deeppockets_archive WHERE cat=10 AND id=294741959 AND type='deeppockets_item' AND published='1' LIMIT 1
154 (422.95455932617): select distinct links.* from jos_textlinks links join jos_textlinks_placement placement on links.id=placement.link_id where journal_id=(10) and (channel_id=212 or channel_id is null)
155 (83.92333984375): select distinct links.* from jos_textlinks links join jos_textlinks_placement placement on links.id=placement.link_id where journal_id=(10) and (channel_id=212 or channel_id is null)
156 (!!!!! 3965.1393890381): SELECT livesite FROM jos_dp_categories WHERE id=10 AND published='1' LIMIT 1
157 (210.04676818848): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294741959 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294741959 AND published='1' LIMIT 1
158 (82.015991210938): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294741959 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294741959 AND published='1' LIMIT 1
159 (61.988830566406): select jos_twitters.link from jos_twitters where cat=10
160 (30.040740966797): select jos_facebook.link from jos_facebook where cat=10
161 (30.994415283203): select jos_google_plus.link from jos_google_plus where cat=10
162 (37.908554077148): select jos_linkedin.link from jos_linkedin where cat=10
163 (283.95652770996): update jos_bannersmanager_banner set impmade=impmade+1 where id in(14615,14202,14203)
164 (!!!!! 1144.1707611084): insert into jos_banners_delta values (14615,'2025-06-26 02:00:49','216.73.216.249','view'),(14202,'2025-06-26 02:00:49','216.73.216.249','view'),(14203,'2025-06-26 02:00:49','216.73.216.249','view')