scholarly journals Neurological deficits in mice with profound biotinidase deficiency are associated with demylination and axonal degeneration

2012 ◽  
Vol 47 (3) ◽  
pp. 428-435 ◽  
Author(s):  
Kirit Pindolia ◽  
Jieli Chen ◽  
Cisley Cardwell ◽  
Xu Cui ◽  
Michael Chopp ◽  
...  
Keyword(s):  
Axonal Degeneration ◽  
Biotinidase Deficiency ◽  
Neurological Deficits

X-linked Adrenoleukodystrophy

2016 ◽  
Author(s):  
Björn M. van Geel ◽  
Marc Engelen ◽  
Stephan Kemp
Keyword(s):  
Axonal Degeneration ◽  
Age Of Onset ◽  
Diagnostic Testing ◽  
Neurological Deficits ◽  
Long Chain Fatty Acids ◽  
Adrenocortical Insufficiency ◽  
Beta Oxidation ◽  
Prenatal Diagnostic ◽  
Prenatal Diagnostic Testing ◽  
Female Carriers

X-linked adrenoleukodystrophy (X-ALD) is the most frequent peroxisomal disorder. Hallmarks are increased levels of plasma very long-chain fatty acids (VLCFA), mutations in the ABCD1 gene, impaired function of ALD-protein and, consequently, decreased import of VLCFA-CoA esters in peroxisomes and VLCFA beta-oxidation. Cerebral demyelination and axonal degeneration of the spinal cord are the main causes of neurological deficits. Endocrine dysfunction, particularly adrenocortical insufficiency, is very frequent. Based upon the age of onset of symptoms and the organs most severely affected, several phenotypes can be distinguished. Adrenomyeloneuropathy (AMN) and childhood cerebral adrenoleukodystrophy (CCALD) are the most frequent variants. At least 80% of female carriers will eventually develop neurological symptoms similar to men with AMN. The thin and scanty scalp hair in affected men may facilitate diagnosis of X-ALD. Identification of patients is of utmost importance, as adrenocortical insufficiency can be treated, rapidly progressive cerebral demyelination can be halted, and prenatal diagnostic testing is available. Furthermore, symptomatic therapies and multidisciplinary support may help patients coping with this disease.

Biotinidase deficiency mimicking neuromyelitis optica: Initially exhibiting symptoms in adulthood

2015 ◽  
Vol 21 (12) ◽  
pp. 1604-1607 ◽  
Author(s):  
Laure Bottin ◽  
Sabine Prud’hon ◽  
Stéphanie Guey ◽  
Claire Giannesini ◽  
Barry Wolf ◽  
...  
Keyword(s):  
Neuromyelitis Optica ◽  
Optic Neuropathy ◽  
Vision Loss ◽  
Biotinidase Deficiency ◽  
Emission Tomography ◽  
Neurological Deficits ◽  
Older Children ◽  
Delayed Onset ◽  
First Case ◽  
Positron Emission

Background: Children with untreated biotinidase deficiency can experience variable symptoms depending on their age of presentation. Older children and adolescents can exhibit predominant neurological deficits including para- or tetraparesis and vision loss. Methods: We report the first case of delayed-onset biotinidase deficiency in a young adult. Results: A 22-year-old man presented with a disabling extensive myelopathy and bilateral optic neuropathy which mimicked the findings of a (seronegative) neuromyelitis optica. Imaging investigations were characterized by an MRI T2 hyper-intensity involving the spinal cord, the optic nerves, the fornix and the mammillar bodies, together with an increased 18F-FDG uptake on positron emission tomography. He was ultimately shown to have profound biotinidase deficiency due to a novel missense mutation and was partly improved by oral biotin therapy. Conclusion: This individual exemplifies the need to include biotinidase deficiency in the differential diagnosis of patients with extensive myelopathy and/or bilateral optic neuropathy and argues for newborn screening for the disorder.

scholarly journals Pharmacological complementation remedies an inborn error of lipid metabolism

2019 ◽  
Author(s):  
Meredith D. Hartley ◽  
Mitra D. Shokat ◽  
Margaret J. DeBell ◽  
Tania Banerji ◽  
Lisa L. Kirkemo ◽  
...  
Keyword(s):  
Thyroid Hormone ◽  
Inborn Error ◽  
Axonal Degeneration ◽  
Parent Drug ◽  
Neurological Deficits ◽  
Long Chain Fatty Acids ◽  
The Central Nervous System ◽  
Cns Penetration ◽  
Long Chain ◽  
Slow Turnover

SummaryX-linked adrenoleukodystrophy (X-ALD) is a rare, genetic disease in which increased very long chain fatty acids (VLCFAs) in the central nervous system (CNS) cause demyelination and axonal degeneration, leading to severe neurological deficits. Sobetirome, a potent thyroid hormone agonist, has been shown to lower VLCFA levels in the periphery and CNS. In this study, two pharmacological strategies for enhancing the effects of thyromimetics were tested in Abcd1 KO mice, a murine model that has the same inborn error in metabolism as X-ALD patients. First, a sobetirome prodrug (Sob-AM2) with increased CNS penetration lowered CNS VLCFAs more potently than sobetirome, and was better tolerated with lower peripheral exposure, but was unable to unable to break the efficacy threshold of CNS VLCFA lowering in Abcd1 KO mice. Second, co-administration of thyroid hormone with sobetirome enhanced VLCFA lowering in the periphery compared to sobetirome alone but did not produce greater lowering in the CNS. These data suggest that the extent of CNS VLCFA lowering in Abcd1 KO mice is limited by a mechanistic threshold related to slow turnover kinetics, potentially related to the lack of frank X-ALD disease in this model. However, Sob-AM2 has improved potency at correcting the lipid abnormality associated with X-ALD in the CNS with better tolerance than the parent drug sobetirome.

β-Mannosidosis: Myelin and oligodendrocyte lesions in brain and spinal cord

1984 ◽  
Vol 42 ◽  
pp. 694-695
Author(s):  
Kathryn L. Lovell ◽  
Margaret Z. Jones
Keyword(s):  
Spinal Cord ◽  
Nervous System ◽  
Genetic Disorder ◽  
Neurological Deficits ◽  
Axonal Spheroids ◽  
South Wales ◽  
Pendular Nystagmus ◽  
Myelin Deficits ◽  
Recessive Defect ◽  
Brain And Spinal Cord

Caprine β-mannosidosis, an autosomal recessive defect of glycoprotein catabolism, is associated with a deficiency of tissue and plasma -mannosidase and with tissue accumulation and urinary excretion of oligosaccharides, including the trisaccharide Man(β1-4)GlcNAc(βl-4)GlcNAc and the disaccharide Man(β1-4)GlcNAc. This genetic disorder is evident at birth, with severe neurological deficits including a marked intention tremor, pendular nystagmus, ataxia and inability to stand. Major pathological characteristics described in Nubian goats in Michigan and in Anglo-Nubian goats in New South Wales include widespread cytoplasmic vacuolation in the nervous system and viscera, axonal spheroids, and severe myelin paucity in the brain but not spinal cord or peripheral nerves. Light microscopic examination revealed marked regional variation in the severity of central nervous system myelin deficits, with some brain areas showing nearly complete absence of myelin and other regions characterized by the presence of 25-50% of the control number of myelin sheaths.

Impairment Tutorial: Neurological Impairment Evaluation: Overview of Sixth Edition Approaches

2008 ◽  
Vol 13 (2) ◽  
pp. 6-8
Author(s):  
Lorne Direnfeld ◽  
Christopher R. Brigham ◽  
Elizabeth Genovese
Keyword(s):  
Spinal Cord ◽  
Neurological Impairment ◽  
Diagnostic Techniques ◽  
Neurological Deficits ◽  
Sixth Edition ◽  
Pain Disability ◽  
Whole Person ◽  
Disability Questionnaire ◽  
Cervical Plating

Abstract The AMA Guides to the Evaluation of Permanent Impairment (AMA Guides), does not provide a Diagnosis-based estimate of impairment due to syringomyelia, a disorder in which a cyst (syrinx), develops within the central spinal cord and destroys neural tissue as it expands. The AMA Guides, however, does provide an approach to rating a syringomyelia based on objective findings of neurological deficits identified during a neurological examination and demonstrated by standard diagnostic techniques. Syringomelia may occur after spinal cord trauma, including a contusion of the cord. A case study illustrates the rating process: The case patient is a 46-year-old male who fell backwards, landing on his upper back and head; over a five-year period he received a T5-6 laminectomy and later partial corpectomies of C5, C6, and C7, cervical discectomy C5-6 and C6-7; iliac crest strut graft fusion of C5-6 and C6-7; and anterior cervical plating of C5 to C7 for treatment of myelopathy; postoperatively, the patient developed dysphagia. The evaluating physician should determine which conditions are ratable, rate each of these components, and combine the resulting whole person impairments without omission or duplication of a ratable impairment. The article includes a pain disability questionnaire that can be used in conjunction with evaluations conducted according to Chapter 3, Pain, and Chapter 17, The Spine.

Microsurgical resection of medullary cavernoma via the olivary zone by the retrosigmoid supracondylar approach

2019 ◽  
Vol 1 (2) ◽  
pp. V7
Author(s):  
Ken Matsushima ◽  
Michihiro Kohno ◽  
Helmut Bertalanffy
Keyword(s):  
Cavernous Malformation ◽  
Cleavage Plane ◽  
Foramen Magnum ◽  
Senior Author ◽  
Neurological Deficits ◽  
Lateral Part ◽  
Sitting Position ◽  
Brainstem Cavernoma ◽  
Microsurgical Resection

Microsurgical resection of the medullary cavernoma is rare, comprising less than 15% of more than 250 surgeries of brainstem cavernoma performed by the senior author (H.B.).1 This video demonstrates a case of a cavernous malformation inside the lateral part of the medulla, which was surgically treated via the olivary zone by the retrosigmoid supracondylar approach in a half-sitting position. Osseous drilling of the lateral foramen magnum provided wide exposure of the cerebellomedullary cistern around the olive.2,3 The lesion was completely dissected at the appropriate cleavage plane from the normal parenchyma. The patient developed no new neurological deficits and had no recurrence during 3 years of follow-up after the operation.The video can be found here: https://youtu.be/7i7SccS5HmU.

Management and outcomes of isolated interhemispheric subdural hematomas associated with falx syndrome

2019 ◽  
Vol 131 (6) ◽  
pp. 1920-1925
Author(s):  
Daniel A. Tonetti ◽  
William J. Ares ◽  
David O. Okonkwo ◽  
Paul A. Gardner
Keyword(s):  
Neurological Deterioration ◽  
Neurological Deficits ◽  
Motor Deficits ◽  
Study Cohort ◽  
Venous Infarction ◽  
Nonsurgical Management ◽  
Subdural Hematomas ◽  
Poor Outcomes ◽  
Contemporary Management

OBJECTIVELarge interhemispheric subdural hematomas (iSDHs) causing falx syndrome are rare; therefore, a paucity of data exists regarding the outcomes of contemporary management of iSDH. There is a general consensus among neurosurgeons that large iSDHs with neurological deficits represent a particular treatment challenge with generally poor outcomes. Thus, radiological and clinical outcomes of surgical and nonsurgical management for iSDH bear further study, which is the aim of this report.METHODSA prospectively collected, single-institution trauma database was searched for patients with isolated traumatic iSDH causing falx syndrome in the period from January 2008 to January 2018. Information on demographic and radiological characteristics, serial neurological examinations, clinical and radiological outcomes, and posttreatment complications was collected and tallied. The authors subsequently dichotomized patients by management strategy to evaluate clinical outcome and 30-day survival.RESULTSTwenty-five patients (0.4% of those with intracranial injuries, 0.05% of those with trauma) with iSDH and falx syndrome represented the study cohort. The average age was 73.4 years, and most patients (23 [92%] of 25) were taking anticoagulants or antiplatelet medications. Six patients were managed nonoperatively, and 19 patients underwent craniotomy for iSDH evacuation; of the latter patients, 17 (89.5%) had improvement in or resolution of motor deficits postoperatively. There were no instances of venous infarction, reaccumulation, or infection after evacuation. In total, 9 (36%) of the 25 patients died within 30 days, including 6 (32%) of the 19 who had undergone craniotomy and 3 (50%) of the 6 who had been managed nonoperatively. Patients who died within 30 days were significantly more likely to experience in-hospital neurological deterioration prior to surgery (83% vs 15%, p = 0.0095) and to be comatose prior to surgery (100% vs 23%, p = 0.0031). The median modified Rankin Scale score of surgical patients who survived hospitalization (13 patients) was 1 at a mean follow-up of 22.1 months.CONCLUSIONSiSDHs associated with falx syndrome can be evacuated safely and effectively, and prompt surgical evacuation prior to neurological deterioration can improve outcomes. In this study, craniotomy for iSDH evacuation proved to be a low-risk strategy that was associated with generally good outcomes, though appropriately selected patients may fare well without evacuation.

Medulla oblongata cavernoma removal through a lazy far lateral approach: operative video and technical nuances

2019 ◽  
Vol 1 (2) ◽  
pp. V21
Author(s):  
Carlos Candanedo ◽  
Samuel Moscovici ◽  
Sergey Spektor
Keyword(s):  
Medulla Oblongata ◽  
Cavernous Malformation ◽  
Complete Removal ◽  
Lateral Approach ◽  
Neurological Deficits ◽  
Total Resection ◽  
Postoperative Mri ◽  
Far Lateral Approach ◽  
Far Lateral ◽  
Brainstem Cavernous Malformation

Removal of brainstem cavernous malformation remains a surgical challenge. We present a case of a 63-year-old female who was diagnosed with a large cavernoma located in the medulla oblongata. The patient suffered three episodes of brainstem bleeding resulting in significant neurological deficits (hemiparesis, dysphagia, and dysarthria). It was decided to remove the cavernoma through a left-sided modified far lateral approach.3The operative video demonstrates the surgical steps and nuances of a complete removal of this complex medulla oblongata cavernous malformation. Total resection was achieved without complications. Postoperative MRI revealed no signs of residual cavernoma with clinical improvement.The video can be found here: https://youtu.be/BTtMvvLMOFM.

The impact of surgeon experience on perioperative complications and operative measures following thoracolumbar 3-column osteotomy for adult spinal deformity: overcoming the learning curve

2020 ◽  
Vol 32 (2) ◽  
pp. 207-220 ◽  
Author(s):  
Darryl Lau ◽  
Vedat Deviren ◽  
Christopher P. Ames
Keyword(s):  
Blood Loss ◽  
Operative Time ◽  
Surgical Complication ◽  
Perioperative Complications ◽  
Adult Spinal Deformity ◽  
Neurological Deficits ◽  
Complication Rates ◽  
Years Of Experience ◽  
Surgeon Experience ◽  
Operative Measures

OBJECTIVEPosterior-based thoracolumbar 3-column osteotomy (3CO) is a formidable surgical procedure. Surgeon experience and case volume are known factors that influence surgical complication rates, but these factors have not been studied well in cases of adult spinal deformity (ASD). This study examines how surgeon experience affects perioperative complications and operative measures following thoracolumbar 3CO in ASD.METHODSA retrospective study was performed of a consecutive cohort of thoracolumbar ASD patients who underwent 3CO performed by the senior authors from 2006 to 2018. Multivariate analysis was used to assess whether experience (years of experience and/or number of procedures) is associated with perioperative complications, operative duration, and blood loss.RESULTSA total of 362 patients underwent 66 vertebral column resections (VCRs) and 296 pedicle subtraction osteotomies (PSOs). The overall complication rate was 29.4%, and the surgical complication rate was 8.0%. The rate of postoperative neurological deficits was 6.2%. There was a trend toward lower overall complication rates with greater operative years of experience (from 44.4% to 28.0%) (p = 0.115). Years of operative experience was associated with a significantly lower rate of neurological deficits (p = 0.027); the incidence dropped from 22.2% to 4.0%. The mean operative time was 310.7 minutes overall. Both increased years of experience and higher case numbers were significantly associated with shorter operative times (p < 0.001 and p = 0.001, respectively). Only operative years of experience was independently associated with operative times (p < 0.001): 358.3 minutes from 2006 to 2008 to 275.5 minutes in 2018 (82.8 minutes shorter). Over time, there was less deviation and more consistency in operative times, despite the implementation of various interventions to promote fusion and prevent construct failure: utilization of multiple-rod constructs (standard, satellite, and nested rods), bone morphogenetic protein, vertebroplasty, and ligament augmentation. Of note, the use of tranexamic acid did not significantly lower blood loss.CONCLUSIONSSurgeon years of experience, rather than number of 3COs performed, was a significant factor in mitigating neurological complications and improving quality measures following thoracolumbar 3CO for ASD. The 3- to 5-year experience mark was when the senior surgeon overcame a learning curve and was able to minimize neurological complication rates. There was a continuous decrease in operative time as the surgeon’s experience increased; this was in concurrence with the implementation of additional preventative surgical interventions. Ongoing practice changes should be implemented and can be done safely, but it is imperative to self-assess the risks and benefits of those practice changes.

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