Cerebrospinal Fluid Parameters in Antisense Oligonucleotide-Treated Adult 5q-Spinal Muscular Atrophy Patients

Approval of nusinersen, an intrathecally administered antisense oligonucleotide, for the treatment of 5q-spinal muscular atrophy (SMA) marked the beginning of a new therapeutic era in neurological diseases. Changes in routine cerebrospinal fluid (CSF) parameters under nusinersen have only recently been described in adult SMA patients. We aimed to explore these findings in a real-world setting and to identify clinical and procedure-associated features that might impact CSF parameters. Routinely collected CSF parameters (leukocyte count, lactate, total protein, CSF/serum albumin quotient (QAlbumin), oligoclonal bands) of 28 adult SMA patients were examined for up to 22 months of nusinersen treatment. Total protein and QAlbumin values significantly increased in the first 10 months, independent of the administration procedure. By month 14, no further increases were detected. Two patients developed transient pleocytosis. In two cases, positive oligoclonal bands were found in the beginning and in four patients throughout the whole observation period. No clinical signs of inflammatory central nervous system disease were apparent. Our data confirm elevated CSF total protein and QAlbumin during nusinersen treatment. These alterations may be caused by both repeated lumbar punctures and the interval between procedures rather than by the medication itself. Generally, there were no severe alterations of CSF routine parameters. These results further underline the safety of nusinersen therapy.

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Inflammatory cerebrospinal fluid analysis in cats: Clinical diagnosis and outcome

Journal of Feline Medicine and Surgery ◽

10.1016/j.jfms.2004.07.001 ◽

2005 ◽

Vol 7 (2) ◽

pp. 77-93 ◽

Cited By ~ 27

Author(s):

M. Singh ◽

D.J. Foster ◽

G. Child ◽

W.A. Lamb

Keyword(s):

Central Nervous System ◽

Cerebrospinal Fluid ◽

Nervous System ◽

Cell Count ◽

Clinical Signs ◽

Central Nervous System Disease ◽

Nervous System Disease ◽

Differential Count ◽

System Disease ◽

Csf Analysis

The medical records of 62 cats with clinical signs of central nervous system disease and accompanying inflammatory cerebrospinal fluid (CSF) analysis were examined retrospectively to determine if signalment, clinical signs, CSF analysis and ancillary testing could accurately predict the type of central nervous system disease that was present. An inflammatory CSF was defined as one in which a total nucleated cell count was greater than 5 cells/μl or one in which the total nucleated cell count was normal but the nucleated cell differential count was abnormal. Sex, degree of CSF inflammation, neuroanatomical location and systemic signs provided little contributory information to the final diagnosis. In 63% of the cases a presumptive diagnosis could be made based on a combination of clinical signs, clinicopathological data and ancillary diagnostic tests. CSF analysis alone was useful only in the diagnosis of cats with feline infectious peritonitis, Cryptococcus species infection, lymphoma and trauma. Overall, despite extensive diagnostic evaluation, a specific diagnosis could not be made in 37% of cats. The prognosis for cats with inflammatory CSF was poor with 77% of cats surviving less than 1 year.

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Antisense Oligonucleotide Therapies for Neurodegenerative Diseases

Annual Review of Neuroscience ◽

10.1146/annurev-neuro-070918-050501 ◽

2019 ◽

Vol 42 (1) ◽

pp. 385-406 ◽

Cited By ~ 41

Author(s):

C. Frank Bennett ◽

Adrian R. Krainer ◽

Don W. Cleveland

Keyword(s):

Neurodegenerative Diseases ◽

Spinal Muscular Atrophy ◽

Antisense Oligonucleotide ◽

Antisense Oligonucleotides ◽

Muscular Atrophy ◽

Neurological Diseases ◽

Great Promise ◽

Disease Symptoms ◽

Therapeutic Platform ◽

Lateral Sclerosis

Antisense oligonucleotides represent a novel therapeutic platform for the discovery of medicines that have the potential to treat most neurodegenerative diseases. Antisense drugs are currently in development for the treatment of amyotrophic lateral sclerosis, Huntington's disease, and Alzheimer's disease, and multiple research programs are underway for additional neurodegenerative diseases. One antisense drug, nusinersen, has been approved for the treatment of spinal muscular atrophy. Importantly, nusinersen improves disease symptoms when administered to symptomatic patients rather than just slowing the progression of the disease. In addition to the benefit to spinal muscular atrophy patients, there are discoveries from nusinersen that can be applied to other neurological diseases, including method of delivery, doses, tolerability of intrathecally delivered antisense drugs, and the biodistribution of intrathecal dosed antisense drugs. Based in part on the early success of nusinersen, antisense drugs hold great promise as a therapeutic platform for the treatment of neurological diseases.

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Testing forBartonellassp. DNA in cerebrospinal fluid of dogs with inflammatory central nervous system disease

Journal of Veterinary Internal Medicine ◽

10.1111/jvim.15288 ◽

2018 ◽

Vol 32 (6) ◽

pp. 1983-1988 ◽

Cited By ~ 3

Author(s):

Lisa R. Bartner ◽

Stephanie McGrath ◽

Adam Drury ◽

Annie V. Chen ◽

Arianne Morris ◽

...

Keyword(s):

Central Nervous System ◽

Cerebrospinal Fluid ◽

Nervous System ◽

Central Nervous System Disease ◽

Nervous System Disease ◽

System Disease

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Dysregulation of microRNAs in spinal muscular atrophy and the response to antisense oligonucleotide therapy

Neuromuscular Disorders ◽

10.1016/j.nmd.2015.06.040 ◽

2015 ◽

Vol 25 ◽

pp. S194

Author(s):

H. Zhou ◽

F. Catapano ◽

I. Zaharieva ◽

M. Scoto ◽

J. Morgan ◽

...

Keyword(s):

Spinal Muscular Atrophy ◽

Antisense Oligonucleotide ◽

Muscular Atrophy ◽

Antisense Oligonucleotide Therapy

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The contribute of cerebrospinal fluid free light-chain assay in the diagnosis of multiple sclerosis and other neurological diseases in an Italian multicenter study

Multiple Sclerosis Journal ◽

10.1177/13524585211064121 ◽

2021 ◽

pp. 135245852110641

Author(s):

Gaetano Bernardi ◽

Tiziana Biagioli ◽

Paola Malpassi ◽

Teresa De Michele ◽

Domizia Vecchio ◽

...

Keyword(s):

Multiple Sclerosis ◽

Cerebrospinal Fluid ◽

Neurological Disorders ◽

Operating Characteristic ◽

Neurological Diseases ◽

Characteristic Curve ◽

Oligoclonal Bands ◽

Free Light Chains ◽

Complementary Information ◽

Combined Use

Background: Cerebrospinal fluid (CSF) free light chains (FLCs) can be an alternative assay to oligoclonal bands (OCBs) in inflammatory neurological disorders, but threshold has no consensus. Objective: To assess the diagnostic accuracy of CSF FLCs in multiple sclerosis (MS) and other neurological diseases. Methods: A total of 406 patients from five Italian centers. FLCs were measured in CSF and serum using Freelite MX assays on Optilite. Results: A total of 171 patients were diagnosed as MS, 154 non-inflammatory neurological diseases, 48 inflammatory central nervous system (CNS) diseases, and 33 peripheral neurological diseases. Both kFLC and λFLC indices were significantly higher in patients with MS compared to other groups ( p < 0.0001). The kFLC index ⩾ 6.4 is comparable to OCB for MS diagnosis (area under the receiver operating characteristic curve (AUC) = 0.876; sensitivity 83.6% vs 84.2%; specificity 88.5% vs 90.6%). λFLC index ⩾ 5 showed an AUC of 0.616, sensitivity of 33.3% and specificity of 90.6%. In all, 12/27 (44.4%) MS patients with negative OCB had kFLC index ⩾ 6.4. Interestingly, 37.5% of 24 patients with a single CSF IgG band showed high kFLC index and 12.5% positive λFLC index. Conclusion: Our findings support the diagnostic utility of FLC indices in MS and other CNS inflammatory disorders, suggesting a combined use of FLC and OCB to help clinicians with complementary information.

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CEREBROSPINAL FLUID LDH IN 287 CHILDREN, INCLUDING 53 CASES OF MENINGITIS OF BACTERIAL AND NON-BACTERIAL ETIOLOGY

PEDIATRICS ◽

10.1542/peds.41.6.1097 ◽

1968 ◽

Vol 41 (6) ◽

pp. 1097-1103

Author(s):

William Neches ◽

Martin Platt

Keyword(s):

Central Nervous System ◽

Cerebrospinal Fluid ◽

Nervous System ◽

Dehydrogenase Activity ◽

Newborn Infants ◽

Central Nervous System Disease ◽

Lactic Dehydrogenase ◽

Spinal Fluid ◽

Initial Examination ◽

System Disease

Cerebrospinal fluid lactic dehydrogenase activity was determined in 287 children. Among these, 87 had no central nervous system disease and were considered to be controls. Mean lactic dehydrogenase activity in 69 controls (excluding newborn infants) was 14 units. In 18 control infants less than 1 week of age, the mean lactic dehydrogenase activity was 50 units. Thirty-two patients with bacterial meningitis had a mean cerebrospinal fluid lactic dehydrogenase of 251 units on the initial examination; 20 patients with aseptic meningoencephalitis had a mean lactic dehydrogenase activity of 23 units. The difference between the lactic dehydrogenase activity in children with bacterial and aseptic meningitis was highly significant (p < 0.005). The clinical course of the patients studied was reflected by the change in cerebrospinal fluid lactic dehydrogenase activity on serial determinations. Spinal fluid isoenzyme patterns were studied in a few patients with bacterial and non-bacterial central nervous system disorders. This study indicates that the determination of lactic dehydrogenase in spinal fluid is a useful adjunct to other cerebrospinal fluid parameters in the differential diagnosis of central nervous system infections.

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