Normal Pressure Hydrocephalus Exacerbation in Multiple Myeloma: Case Report

Normal Pressure Hydrocephalus Exacerbation in Multiple Myeloma: Case Report | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Case Report Normal Pressure Hydrocephalus Exacerbation in Multiple Myeloma: Case Report Robert Fekete This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-6430094/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Background Neurological complications of multiple myeloma typically include light chain related peripheral neuropathy, hypercalcemia, amyloidosis, and hyperviscosity syndrome. Central nervous system involvement in multiple myeloma is rare. Possible routes of involvement include direct osseous spread or hematogenous spread of extra medullary disease. There can also be effects due to elevated cerebrospinal fluid (CSF) protein levels and subsequent increase of CSF pressure, either from proteins produced by myeloma itself or from blood brain barrier dysfunction and leakage of serum protein into CSF space. Case report The patient is a 76-year-old white female who presented with three years of magnetic gait as well as imbalance. She was able to control urination, but would have urge incontinence if she was too slow to walk to the bathroom. She reported no relevant family history. There was no smoking history. Her past surgical history is hysterectomy. She was alert and oriented to person, place, and time. Her delayed recall was 3/3. She exhibited unsteady, wide based, magnetic gait. Her neurological examination was otherwise normal. Initial lumbar puncture was normal. There was no improvement of gait after lumbar puncture. Carbidopa levodopa 25/100 mg tablets three times a day led to no improvement. She was subsequently diagnosed with smoldering multiple myeloma given 30% plasma cells in bone marrow which were Kappa and CD138 positive and after drop in hemoglobin and platelet was placed on daratumab regimen for IgA Kappa multiple myeloma. One year after the initial evaluation, she was evaluated in the emergency room with inability to ambulate, confusion, and urinary incontinence. As her platelets recovered to normal, lumbar puncture was performed, showing opening pressure of 60 cm H20, Protein >4,000 mg/dl (normal 15-45 mg/dl), but with negative CSF cytology. Pleural fluid cytology revealed plasma cells. She received further chemotherapy with return of normal mental status but remains with urinary incontinence and unable to ambulate. Discussion Possible CNS involvement by myeloma was implied from worsening gait disturbance and elevated CSF protein. IgA myeloma is more likely to have CNS involvement but she doesn’t formally qualify for Bing Neely syndrome given absence of proof of plasma cells in the cerebrospinal fluid. It is possible that her neurological symptoms were due to blood brain barrier dysfunction. Oncology Normal pressure hydrocephalus magnetic gait multiple myeloma Figures Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Background Neurological complications of multiple myeloma typically include light chain related peripheral neuropathy, hypercalcemia, amyloidosis, and hyperviscosity syndrome. Central nervous system involvement in multiple myeloma is rare. Possible routes of involvement include direct osseous spread or hematogenous spread of extra medullary disease [ 1 ]. There can also be effects due to elevated cerebrospinal fluid (CSF) protein levels and subsequent increase of CSF pressure, either from proteins produced by myeloma itself or from blood brain barrier dysfunction and leakage of serum protein into CSF space [ 2 ]. Case report The patient is a 76-year-old white female who presented with three years of magnetic gait as well as imbalance. She was able to control urination, but would have urge incontinence if she was too slow to walk to the bathroom. She reported no relevant family history. There was no smoking history. Her past surgical history is hysterectomy. She was alert and oriented to person, place, and time. Her delayed recall was 3/3. She exhibited unsteady, wide based, magnetic gait. Her neurological examination was otherwise normal. Magnetic resonance imaging (MRI) demonstrated ventriculomegaly (Fig. 1) and ballooning of the third ventricle (Fig. 2). Lumbar puncture was performed which was normal. Opening pressure was 19 cm H 2 0, closing pressure was 10 cm H 2 0. Cerebrospinal fluid (CSF) protein was 30 (normal 15–45), CSF glucose was 62 (normal 40–70), CSF white blood cell count was zero, and CSF red blood cell count was 3 per mm 3 (normal 0–5 cells per mm 3 ). Serum was significant for Kappa free light chains elevated to 32.8 mg/L (normal 3.3–19.4 mg/L), with free light chain ratio of 5.08 (normal 0.26–1.65). Serum calcium was slightly elevated to 10.3 mg/dl (normal 8.6–10.2 mg/dl). Alkaline phosphatase was elevated to 174 U/L (normal 40–150 U/L). There was no improvement of gait after lumbar puncture. Carbidopa levodopa 25/100 mg tablets three times a day was attempted and also led to no improvement. Patient stopped this medication after 3 doses due to lightheadedness and palpitations, likely due to hypotension. Bone marrow biopsy was performed which revealed hypercellularity with 30 percent plasma cells which were CD138 and Kappa positive. She was diagnosed with smoldering IgA Kappa multiple myeloma. Positron emission tomography – computer tomography was significant for calvarial lesion, severe ventriculomegaly, and hypermetabolic thyroid lesion. 8 months after the initial evaluation, she presented to an emergency room with nausea. Laboratory studies revealed drop in hemoglobin to 9.7 g/dl from 14.5 g/dl as well as in platelets to about 50,000 per mm 3 . White blood cell count was 9000 per mm 3 . Repeat bone marrow biopsy showed 95 percent plasma cells consistent with IgA Kappa multiple myeloma. Bone marrow plasma cells were positive for Kappa and CD138 as well as negative for Congo red stain. Serum M protein increased to 1.5 g/dl (from 0.27 g/dl). Kappa light chain increased to 73 mg/L (normal 3.3–19.4 mg/L). IgA level increased to 1681 mg/dl (normal 43–383 mg/dl). Bone marrow fluorescence in site hybridization analysis was negative for Chromosome 8, Chromosome 20, Chromosome 5 tricolor, Chromosome 7q tricolor, or 11q23 abnormalities. She was placed on daratumumab regimen weekly for 8 weeks with dexamethasone 4 mg daily except for 16 mg on daratumumab days. Subsequently, she received daratumumab every 2 weeks for one month. One year after the initial evaluation, she was evaluated in the emergency room with inability to ambulate, intermittent confusion, and urinary incontinence. As her platelets recovered to normal, lumbar puncture was performed, showing opening pressure of 60 cm H20, 20 ml aspirated, closing pressure 13 cm H2O, CSF protein > 4,000 mg/dl (normal 15–45 mg/dl), CSF glucose was 221 mg/dl (normal 40–70 mg/dl), CSF white blood cell count was 4 / mm 3 (normal 0–5 cells/mm 3 ) with Lymphocytes 41%, Monocytes 8%, polynucleated cells 51%. and CSF red blood cell count was 594 per mm 3 (normal 0–5 cells per mm 3 ). Serum glucose was 222 mg/dl. Even with correction factor in traumatic lumbar puncture of CSF protein level increase of 1.1 mg/dL for every 1000-cell increase in CSF RBC count, the patient still had markedly elevated CSF protein [ 1 ]. Lactate dehydrogenase was 653 U/L (normal 125–220 U/L). Cytology from CSF was negative. There was no improvement of her inability to walk after the lumbar puncture. Cytology of the CSF was acellular. Patient had bilateral large pleural effusions with nodular pleural thickening and soft tissue masses along the ribs and chest wall (Fig. 3). Pleural fluid cytopathology showed plasma cells with prominent nucleoli, binucleation consistent with multiple myeloma. Flow cytometry of pleural fluid showed cytoplasmic kappa clonal cell population with high forward and side scatter (81% of total) expressing CD38 (dim), CD138, and CD56. Immunohistochemical stains of pleural fluid cytology were positive for CD138 and kappa while negative for CD117 and lambda. There were infiltrating soft tissue masses along the right and left iliac crest (Fig. 4). At time of writing, patient has been treated with cyclophosphamide (300 mg/m2 orally weekly), bortezomib (1.5 mg/m2 weekly), and dexamethasone (40 mg weekly) (CyBorD) for 6 months with maintenance of normal mental status but without improvement of urinary incontinence and inability to walk. Case report The patient is a 76-year-old white female who presented with three years of magnetic gait as well as imbalance. She was able to control urination, but would have urge incontinence if she was too slow to walk to the bathroom. She reported no relevant family history. There was no smoking history. Her past surgical history is hysterectomy. She was alert and oriented to person, place, and time. Her delayed recall was 3/3. She exhibited unsteady, wide based, magnetic gait. Her neurological examination was otherwise normal. Magnetic resonance imaging (MRI) demonstrated ventriculomegaly (Fig. 1) and ballooning of the third ventricle (Fig. 2). Lumbar puncture was performed which was normal. Opening pressure was 19 cm H 2 0, closing pressure was 10 cm H 2 0. Cerebrospinal fluid (CSF) protein was 30 (normal 15–45), CSF glucose was 62 (normal 40–70), CSF white blood cell count was zero, and CSF red blood cell count was 3 per mm 3 (normal 0–5 cells per mm 3 ). Serum was significant for Kappa free light chains elevated to 32.8 mg/L (normal 3.3–19.4 mg/L), with free light chain ratio of 5.08 (normal 0.26–1.65). Serum calcium was slightly elevated to 10.3 mg/dl (normal 8.6–10.2 mg/dl). Alkaline phosphatase was elevated to 174 U/L (normal 40–150 U/L). There was no improvement of gait after lumbar puncture. Carbidopa levodopa 25/100 mg tablets three times a day was attempted and also led to no improvement. Patient stopped this medication after 3 doses due to lightheadedness and palpitations, likely due to hypotension. Bone marrow biopsy was performed which revealed hypercellularity with 30 percent plasma cells which were CD138 and Kappa positive. She was diagnosed with smoldering IgA Kappa multiple myeloma. Positron emission tomography – computer tomography was significant for calvarial lesion, severe ventriculomegaly, and hypermetabolic thyroid lesion. 8 months after the initial evaluation, she presented to an emergency room with nausea. Laboratory studies revealed drop in hemoglobin to 9.7 g/dl from 14.5 g/dl as well as in platelets to about 50,000 per mm 3 . White blood cell count was 9000 per mm 3 . Repeat bone marrow biopsy showed 95 percent plasma cells consistent with IgA Kappa multiple myeloma. Bone marrow plasma cells were positive for Kappa and CD138 as well as negative for Congo red stain. Serum M protein increased to 1.5 g/dl (from 0.27 g/dl). Kappa light chain increased to 73 mg/L (normal 3.3–19.4 mg/L). IgA level increased to 1681 mg/dl (normal 43–383 mg/dl). Bone marrow fluorescence in site hybridization analysis was negative for Chromosome 8, Chromosome 20, Chromosome 5 tricolor, Chromosome 7q tricolor, or 11q23 abnormalities. She was placed on daratumumab regimen weekly for 8 weeks with dexamethasone 4 mg daily except for 16 mg on daratumumab days. Subsequently, she received daratumumab every 2 weeks for one month. One year after the initial evaluation, she was evaluated in the emergency room with inability to ambulate, intermittent confusion, and urinary incontinence. As her platelets recovered to normal, lumbar puncture was performed, showing opening pressure of 60 cm H20, 20 ml aspirated, closing pressure 13 cm H2O, CSF protein > 4,000 mg/dl (normal 15–45 mg/dl), CSF glucose was 221 mg/dl (normal 40–70 mg/dl), CSF white blood cell count was 4 / mm 3 (normal 0–5 cells/mm 3 ) with Lymphocytes 41%, Monocytes 8%, polynucleated cells 51%. and CSF red blood cell count was 594 per mm 3 (normal 0–5 cells per mm 3 ). Serum glucose was 222 mg/dl. Even with correction factor in traumatic lumbar puncture of CSF protein level increase of 1.1 mg/dL for every 1000-cell increase in CSF RBC count, the patient still had markedly elevated CSF protein [ 1 ]. Lactate dehydrogenase was 653 U/L (normal 125–220 U/L). Cytology from CSF was negative. There was no improvement of her inability to walk after the lumbar puncture. Cytology of the CSF was acellular. Patient had bilateral large pleural effusions with nodular pleural thickening and soft tissue masses along the ribs and chest wall (Fig. 3). Pleural fluid cytopathology showed plasma cells with prominent nucleoli, binucleation consistent with multiple myeloma. Flow cytometry of pleural fluid showed cytoplasmic kappa clonal cell population with high forward and side scatter (81% of total) expressing CD38 (dim), CD138, and CD56. Immunohistochemical stains of pleural fluid cytology were positive for CD138 and kappa while negative for CD117 and lambda. There were infiltrating soft tissue masses along the right and left iliac crest (Fig. 4). At time of writing, patient has been treated with cyclophosphamide (300 mg/m2 orally weekly), bortezomib (1.5 mg/m2 weekly), and dexamethasone (40 mg weekly) (CyBorD) for 6 months with maintenance of normal mental status but without improvement of urinary incontinence and inability to walk. Discussion Possible CNS involvement by myeloma was considered from worsening gait disturbance and elevated CSF protein. Potential route of entry to CNS was from calvarial lesion (Figure 5) or hematogenous spread. As CSF cytology was negative for plasma cells, there is no direct proof of CNS invasion. She doesn’t formally qualify for Bing Neely syndrome given absence of proof of plasma cells in the cerebrospinal fluid. IgA myeloma is more likely to have CNS involvement. Loss of CD53 is reported to facilitate escape of myeloma cells into the CSF. CD53 expression was present in the pleural fluid specimen. Significantly elevated CSF protein may still be due to CSF metastasis that could not be shown, but it could also be due to blood brain barrier dysfunction [2]. Impairment of blood brain barrier could have caused serum protein leakage into CSF space. Obstruction of CSF outflow could be caused by local protein complexes, inflammation, or direct mass effect for example at the cribriform plate. Declarations Patient perspective The patient appreciates the opportunity to share information about the unusual aspects of her multiple myeloma case. Acknowledgements None. Consensus-based Clinical Case Reporting (CARE) Guidelines were used [4]. Ethics approval and consent to participate Written informed consent was obtained from the patient for participation in this case report however, no ethical approval was needed. "The institution’s policy, therefore, is that a case report is not research that must be approved by the IRB." New York Medical College Policies and Procedures for the Conduct of Research Involving Human Subjects. [https://www.nymc.edu/media/schools-andcolleges/nymc/pdf/human-subjects-research/IRBmanual.pdf] Accessed on 3/24/2025. Consent for publication Written informed consent was obtained from the patient for publication of this case report and any accompanying images. A copy of the written consent is available for review by the Editor-in-Chief of this journal. Availability of data All supporting data were included in this manuscript. Patient clinical data is protected by the United States Health Insurance Portability and Accountability Act (HIPAA) of 1996. Competing interests The author declares that he does not have any competing interests Funding None. Author contributions RF: conception, data acquisition, writing, and revising References Fitzgerald E, Kiely P, Leary H (2019) Intracranial Involvement in Multiple Myeloma Presenting as a Cranial Nerve Palsy. J Hematol 8(1):29–33 Chantran Y, Lavillegrand JR, Lefrere B et al (2019) Multiple myeloma with clivus involvement, neurological symptoms, and 45 g/L proteinorachia. Clin Case Rep 8(1):5–8. 10.1002/ccr3.2404 Nigrovic LE et al (2011) Correction of cerebrospinal fluid protein for the presence of red blood cells in children with a traumatic lumbar puncture. J Pediatr 159:158 Gagnier JJ, Kienle G, Altman DG, Moher D, Sox H, Riley D, the CARE Group. The CARE Guidelines: Consensus-based Clinical Case Reporting Guideline Development Additional Declarations The authors declare no competing interests. Supplementary Files completedCAREchecklist.docx Supplementary File 1: Completed CARE checklist Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-6430094","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Case Report","associatedPublications":[],"authors":[{"id":441802975,"identity":"e7343093-faff-4544-9f9b-30cc6720f26b","order_by":0,"name":"Robert 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ventriculomegaly\u003c/p\u003e","description":"","filename":"figure1ventriculomegaly.png","url":"https://assets-eu.researchsquare.com/files/rs-6430094/v1/4fc7bbcfba37f4ee91e03479.png"},{"id":80727540,"identity":"3bf17c33-e306-40a8-8c32-d474c93f1484","added_by":"auto","created_at":"2025-04-16 12:02:31","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":1025670,"visible":true,"origin":"","legend":"\u003cp\u003eAxial (MRI) image showing ballooning of the third ventricle (green arrow)\u003c/p\u003e","description":"","filename":"figure2balooningofthirdventricle.png","url":"https://assets-eu.researchsquare.com/files/rs-6430094/v1/7e97996e89b28ab5b5c8f0f5.png"},{"id":80728571,"identity":"e19eb756-0e5c-4ded-a5eb-8a7ad1a691dc","added_by":"auto","created_at":"2025-04-16 12:10:31","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":992808,"visible":true,"origin":"","legend":"\u003cp\u003eBilateral large pleural effusions with nodular pleural thickening and soft tissue masses along the ribs and chest wall (green circle).\u003c/p\u003e","description":"","filename":"figure3softtissuemasschest.png","url":"https://assets-eu.researchsquare.com/files/rs-6430094/v1/459e0be77fb988074aefcc48.png"},{"id":80728572,"identity":"388ba9c3-99f0-48fa-8c26-6d66b6236341","added_by":"auto","created_at":"2025-04-16 12:10:31","extension":"png","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":1467977,"visible":true,"origin":"","legend":"\u003cp\u003eInfiltrating soft tissue masses along right and left (green arrow) iliac crest\u003c/p\u003e","description":"","filename":"figure4infiltratingsofttissueiliacbone.png","url":"https://assets-eu.researchsquare.com/files/rs-6430094/v1/2c1d895447a79a04dd3ae8c8.png"},{"id":80727542,"identity":"c2fa486a-597b-4580-9c65-c35989f02d28","added_by":"auto","created_at":"2025-04-16 12:02:31","extension":"png","order_by":5,"title":"Figure 5","display":"","copyAsset":false,"role":"figure","size":1071205,"visible":true,"origin":"","legend":"\u003cp\u003ePost contrast T2 coronal MRI showing enhancing hyperintense right calvarial lesion (green arrow)\u003c/p\u003e","description":"","filename":"figure5t2hyperintenselesionrightcalvarium.png","url":"https://assets-eu.researchsquare.com/files/rs-6430094/v1/f54c7ad0889fc64f7a03b4f1.png"},{"id":80728576,"identity":"04f18b69-e528-45a6-9df6-931e563a2cbd","added_by":"auto","created_at":"2025-04-16 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Report\u003c/p\u003e","fulltext":[{"header":"Background","content":"\u003cp\u003eNeurological complications of multiple myeloma typically include light chain related peripheral neuropathy, hypercalcemia, amyloidosis, and hyperviscosity syndrome. Central nervous system involvement in multiple myeloma is rare. Possible routes of involvement include direct osseous spread or hematogenous spread of extra medullary disease [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]. There can also be effects due to elevated cerebrospinal fluid (CSF) protein levels and subsequent increase of CSF pressure, either from proteins produced by myeloma itself or from blood brain barrier dysfunction and leakage of serum protein into CSF space [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e].\u003c/p\u003e \u003cp name=\"removable\"\u003eCase report\u003c/p\u003e \u003cp name=\"removable\"\u003eThe patient is a 76-year-old white female who presented with three years of magnetic gait as well as imbalance. She was able to control urination, but would have urge incontinence if she was too slow to walk to the bathroom. She reported no relevant family history. There was no smoking history. Her past surgical history is hysterectomy. She was alert and oriented to person, place, and time. Her delayed recall was 3/3. She exhibited unsteady, wide based, magnetic gait. Her neurological examination was otherwise normal. Magnetic resonance imaging (MRI) demonstrated ventriculomegaly (Fig.\u0026nbsp;1) and ballooning of the third ventricle (Fig.\u0026nbsp;2).\u003c/p\u003e \u003cp name=\"removable\"\u003eLumbar puncture was performed which was normal. Opening pressure was 19 cm H\u003csub\u003e2\u003c/sub\u003e0, closing pressure was 10 cm H\u003csub\u003e2\u003c/sub\u003e0. Cerebrospinal fluid (CSF) protein was 30 (normal 15–45), CSF glucose was 62 (normal 40–70), CSF white blood cell count was zero, and CSF red blood cell count was 3 per mm\u003csup\u003e3\u003c/sup\u003e (normal 0–5 cells per mm\u003csup\u003e3\u003c/sup\u003e). Serum was significant for Kappa free light chains elevated to 32.8 mg/L (normal 3.3–19.4 mg/L), with free light chain ratio of 5.08 (normal 0.26–1.65). Serum calcium was slightly elevated to 10.3 mg/dl (normal 8.6–10.2 mg/dl). Alkaline phosphatase was elevated to 174 U/L (normal 40–150 U/L).\u003c/p\u003e \u003cp name=\"removable\"\u003eThere was no improvement of gait after lumbar puncture. Carbidopa levodopa 25/100 mg tablets three times a day was attempted and also led to no improvement. Patient stopped this medication after 3 doses due to lightheadedness and palpitations, likely due to hypotension.\u003c/p\u003e \u003cp name=\"removable\"\u003eBone marrow biopsy was performed which revealed hypercellularity with 30 percent plasma cells which were CD138 and Kappa positive. She was diagnosed with smoldering IgA Kappa multiple myeloma. Positron emission tomography – computer tomography was significant for calvarial lesion, severe ventriculomegaly, and hypermetabolic thyroid lesion.\u003c/p\u003e \u003cp name=\"removable\"\u003e8 months after the initial evaluation, she presented to an emergency room with nausea. Laboratory studies revealed drop in hemoglobin to 9.7 g/dl from 14.5 g/dl as well as in platelets to about 50,000 per mm\u003csup\u003e3\u003c/sup\u003e. White blood cell count was 9000 per mm\u003csup\u003e3\u003c/sup\u003e. Repeat bone marrow biopsy showed 95 percent plasma cells consistent with IgA Kappa multiple myeloma. Bone marrow plasma cells were positive for Kappa and CD138 as well as negative for Congo red stain. Serum M protein increased to 1.5 g/dl (from 0.27 g/dl). Kappa light chain increased to 73 mg/L (normal 3.3–19.4 mg/L). IgA level increased to 1681 mg/dl (normal 43–383 mg/dl). Bone marrow fluorescence in site hybridization analysis was negative for Chromosome 8, Chromosome 20, Chromosome 5 tricolor, Chromosome 7q tricolor, or 11q23 abnormalities.\u003c/p\u003e \u003cp name=\"removable\"\u003eShe was placed on daratumumab regimen weekly for 8 weeks with dexamethasone 4 mg daily except for 16 mg on daratumumab days. Subsequently, she received daratumumab every 2 weeks for one month.\u003c/p\u003e \u003cp name=\"removable\"\u003eOne year after the initial evaluation, she was evaluated in the emergency room with inability to ambulate, intermittent confusion, and urinary incontinence. As her platelets recovered to normal, lumbar puncture was performed, showing opening pressure of 60 cm H20, 20 ml aspirated, closing pressure 13 cm H2O, CSF protein \u0026gt; 4,000 mg/dl (normal 15–45 mg/dl), CSF glucose was 221 mg/dl (normal 40–70 mg/dl), CSF white blood cell count was 4 / mm\u003csup\u003e3\u003c/sup\u003e (normal 0–5 cells/mm\u003csup\u003e3\u003c/sup\u003e) with Lymphocytes 41%, Monocytes 8%, polynucleated cells 51%. and CSF red blood cell count was 594 per mm\u003csup\u003e3\u003c/sup\u003e (normal 0–5 cells per mm\u003csup\u003e3\u003c/sup\u003e). Serum glucose was 222 mg/dl. Even with correction factor in traumatic lumbar puncture of CSF protein level increase of 1.1 mg/dL for every 1000-cell increase in CSF RBC count, the patient still had markedly elevated CSF protein [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]. Lactate dehydrogenase was 653 U/L (normal 125–220 U/L). Cytology from CSF was negative. There was no improvement of her inability to walk after the lumbar puncture.\u003c/p\u003e \u003cp name=\"removable\"\u003eCytology of the CSF was acellular. Patient had bilateral large pleural effusions with nodular pleural thickening and soft tissue masses along the ribs and chest wall (Fig.\u0026nbsp;3). Pleural fluid cytopathology showed plasma cells with prominent nucleoli, binucleation consistent with multiple myeloma. Flow cytometry of pleural fluid showed cytoplasmic kappa clonal cell population with high forward and side scatter (81% of total) expressing CD38 (dim), CD138, and CD56. Immunohistochemical stains of pleural fluid cytology were positive for CD138 and kappa while negative for CD117 and lambda. There were infiltrating soft tissue masses along the right and left iliac crest (Fig.\u0026nbsp;4).\u003c/p\u003e \u003cp name=\"removable\"\u003eAt time of writing, patient has been treated with cyclophosphamide (300 mg/m2 orally weekly), bortezomib (1.5 mg/m2 weekly), and dexamethasone (40 mg weekly) (CyBorD) for 6 months with maintenance of normal mental status but without improvement of urinary incontinence and inability to walk.\u003c/p\u003e"},{"header":"Case report","content":"\u003cp\u003eThe patient is a 76-year-old white female who presented with three years of magnetic gait as well as imbalance. She was able to control urination, but would have urge incontinence if she was too slow to walk to the bathroom. She reported no relevant family history. There was no smoking history. Her past surgical history is hysterectomy. She was alert and oriented to person, place, and time. Her delayed recall was 3/3. She exhibited unsteady, wide based, magnetic gait. Her neurological examination was otherwise normal. Magnetic resonance imaging (MRI) demonstrated ventriculomegaly (Fig.\u0026nbsp;1) and ballooning of the third ventricle (Fig.\u0026nbsp;2).\u003c/p\u003e\u003cp\u003eLumbar puncture was performed which was normal. Opening pressure was 19 cm H\u003csub\u003e2\u003c/sub\u003e0, closing pressure was 10 cm H\u003csub\u003e2\u003c/sub\u003e0. Cerebrospinal fluid (CSF) protein was 30 (normal 15–45), CSF glucose was 62 (normal 40–70), CSF white blood cell count was zero, and CSF red blood cell count was 3 per mm\u003csup\u003e3\u003c/sup\u003e (normal 0–5 cells per mm\u003csup\u003e3\u003c/sup\u003e). Serum was significant for Kappa free light chains elevated to 32.8 mg/L (normal 3.3–19.4 mg/L), with free light chain ratio of 5.08 (normal 0.26–1.65). Serum calcium was slightly elevated to 10.3 mg/dl (normal 8.6–10.2 mg/dl). Alkaline phosphatase was elevated to 174 U/L (normal 40–150 U/L).\u003c/p\u003e\u003cp\u003eThere was no improvement of gait after lumbar puncture. Carbidopa levodopa 25/100 mg tablets three times a day was attempted and also led to no improvement. Patient stopped this medication after 3 doses due to lightheadedness and palpitations, likely due to hypotension.\u003c/p\u003e\u003cp\u003eBone marrow biopsy was performed which revealed hypercellularity with 30 percent plasma cells which were CD138 and Kappa positive. She was diagnosed with smoldering IgA Kappa multiple myeloma. Positron emission tomography – computer tomography was significant for calvarial lesion, severe ventriculomegaly, and hypermetabolic thyroid lesion.\u003c/p\u003e\u003cp\u003e8 months after the initial evaluation, she presented to an emergency room with nausea. Laboratory studies revealed drop in hemoglobin to 9.7 g/dl from 14.5 g/dl as well as in platelets to about 50,000 per mm\u003csup\u003e3\u003c/sup\u003e. White blood cell count was 9000 per mm\u003csup\u003e3\u003c/sup\u003e. Repeat bone marrow biopsy showed 95 percent plasma cells consistent with IgA Kappa multiple myeloma. Bone marrow plasma cells were positive for Kappa and CD138 as well as negative for Congo red stain. Serum M protein increased to 1.5 g/dl (from 0.27 g/dl). Kappa light chain increased to 73 mg/L (normal 3.3–19.4 mg/L). IgA level increased to 1681 mg/dl (normal 43–383 mg/dl). Bone marrow fluorescence in site hybridization analysis was negative for Chromosome 8, Chromosome 20, Chromosome 5 tricolor, Chromosome 7q tricolor, or 11q23 abnormalities.\u003c/p\u003e\u003cp\u003eShe was placed on daratumumab regimen weekly for 8 weeks with dexamethasone 4 mg daily except for 16 mg on daratumumab days. Subsequently, she received daratumumab every 2 weeks for one month.\u003c/p\u003e\u003cp\u003eOne year after the initial evaluation, she was evaluated in the emergency room with inability to ambulate, intermittent confusion, and urinary incontinence. As her platelets recovered to normal, lumbar puncture was performed, showing opening pressure of 60 cm H20, 20 ml aspirated, closing pressure 13 cm H2O, CSF protein \u0026gt; 4,000 mg/dl (normal 15–45 mg/dl), CSF glucose was 221 mg/dl (normal 40–70 mg/dl), CSF white blood cell count was 4 / mm\u003csup\u003e3\u003c/sup\u003e (normal 0–5 cells/mm\u003csup\u003e3\u003c/sup\u003e) with Lymphocytes 41%, Monocytes 8%, polynucleated cells 51%. and CSF red blood cell count was 594 per mm\u003csup\u003e3\u003c/sup\u003e (normal 0–5 cells per mm\u003csup\u003e3\u003c/sup\u003e). Serum glucose was 222 mg/dl. Even with correction factor in traumatic lumbar puncture of CSF protein level increase of 1.1 mg/dL for every 1000-cell increase in CSF RBC count, the patient still had markedly elevated CSF protein [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]. Lactate dehydrogenase was 653 U/L (normal 125–220 U/L). Cytology from CSF was negative. There was no improvement of her inability to walk after the lumbar puncture.\u003c/p\u003e\u003cp\u003eCytology of the CSF was acellular. Patient had bilateral large pleural effusions with nodular pleural thickening and soft tissue masses along the ribs and chest wall (Fig.\u0026nbsp;3). Pleural fluid cytopathology showed plasma cells with prominent nucleoli, binucleation consistent with multiple myeloma. Flow cytometry of pleural fluid showed cytoplasmic kappa clonal cell population with high forward and side scatter (81% of total) expressing CD38 (dim), CD138, and CD56. Immunohistochemical stains of pleural fluid cytology were positive for CD138 and kappa while negative for CD117 and lambda. There were infiltrating soft tissue masses along the right and left iliac crest (Fig.\u0026nbsp;4).\u003c/p\u003e\u003cp\u003eAt time of writing, patient has been treated with cyclophosphamide (300 mg/m2 orally weekly), bortezomib (1.5 mg/m2 weekly), and dexamethasone (40 mg weekly) (CyBorD) for 6 months with maintenance of normal mental status but without improvement of urinary incontinence and inability to walk.\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003ePossible CNS involvement by myeloma was considered from worsening gait disturbance and elevated CSF protein. Potential route of entry to CNS was from calvarial lesion (Figure 5) or hematogenous spread. As CSF cytology was negative for plasma cells, there is no direct proof of CNS invasion. She doesn\u0026rsquo;t formally qualify for Bing Neely syndrome given absence of proof of plasma cells in the cerebrospinal fluid. IgA myeloma is more likely to have CNS involvement. Loss of CD53 is reported to facilitate escape of myeloma cells into the CSF. CD53 expression was present in the pleural fluid specimen.\u003c/p\u003e\n\u003cp\u003eSignificantly elevated CSF protein may still be due to CSF metastasis that could not be shown, but it could also be due to blood brain barrier dysfunction [2]. \u0026nbsp;Impairment of blood brain barrier could have caused serum protein leakage into CSF space. Obstruction of CSF outflow could be caused by local protein complexes, inflammation, or direct mass effect for example at the cribriform plate.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003ePatient perspective\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe patient appreciates the opportunity to share information about the unusual aspects of her multiple myeloma case.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAcknowledgements\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNone.\u003c/p\u003e\n\u003cp\u003eConsensus-based Clinical Case Reporting (CARE) Guidelines were used [4].\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eEthics approval and consent to participate\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eWritten informed consent was obtained from the patient for participation in this case report however, no ethical approval was needed.\u003c/p\u003e\n\u003cp\u003e\u0026quot;The institution\u0026rsquo;s policy, therefore, is that a case report is not research that must be approved by the IRB.\u0026quot;\u003c/p\u003e\n\u003cp\u003eNew York Medical College Policies and Procedures for the Conduct of Research\u003c/p\u003e\n\u003cp\u003eInvolving Human Subjects. [https://www.nymc.edu/media/schools-andcolleges/nymc/pdf/human-subjects-research/IRBmanual.pdf] Accessed on 3/24/2025.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent for publication\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eWritten informed consent was obtained from the patient for publication of this case report and any accompanying images. A copy of the written consent is available for review by the Editor-in-Chief of this journal.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAvailability of data\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAll supporting data were included in this manuscript. Patient clinical data is protected by the United States Health Insurance Portability and Accountability Act (HIPAA) of 1996.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting interests\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe author declares that he does not have any competing interests\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNone.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthor contributions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eRF: conception, data acquisition, writing, and revising\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eFitzgerald E, Kiely P, Leary H (2019) Intracranial Involvement in Multiple Myeloma Presenting as a Cranial Nerve Palsy. J Hematol 8(1):29\u0026ndash;33\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eChantran Y, Lavillegrand JR, Lefrere B et al (2019) Multiple myeloma with clivus involvement, neurological symptoms, and 45 g/L proteinorachia. Clin Case Rep 8(1):5\u0026ndash;8. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1002/ccr3.2404\u003c/span\u003e\u003cspan address=\"10.1002/ccr3.2404\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eNigrovic LE et al (2011) Correction of cerebrospinal fluid protein for the presence of red blood cells in children with a traumatic lumbar puncture. J Pediatr 159:158\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eGagnier JJ, Kienle G, Altman DG, Moher D, Sox H, Riley D, the CARE Group. The CARE Guidelines: Consensus-based Clinical Case Reporting Guideline Development\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":true,"hideJournal":true,"highlight":"","institution":"New York Medical College","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"Normal pressure hydrocephalus, magnetic gait, multiple myeloma","lastPublishedDoi":"10.21203/rs.3.rs-6430094/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-6430094/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003eBackground\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNeurological complications of multiple myeloma typically include light chain related peripheral neuropathy, hypercalcemia, amyloidosis, and hyperviscosity syndrome. Central nervous system involvement in multiple myeloma is rare. Possible routes of involvement include direct osseous spread or hematogenous spread of extra medullary disease. There can also be effects due to elevated cerebrospinal fluid (CSF) protein levels and subsequent increase of CSF pressure, either from proteins produced by myeloma itself or from blood brain barrier dysfunction and leakage of serum protein into CSF space.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCase report\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe patient is a 76-year-old white female who presented with three years of magnetic gait as well as imbalance. She was able to control urination, but would have urge incontinence if she was too slow to walk to the bathroom. She reported no relevant family history. There was no smoking history. Her past surgical history is hysterectomy. She was alert and oriented to person, place, and time. Her delayed recall was 3/3. She exhibited unsteady, wide based, magnetic gait. Her neurological examination was otherwise normal.\u003c/p\u003e\n\u003cp\u003eInitial lumbar puncture was normal. There was no improvement of gait after lumbar puncture. Carbidopa levodopa 25/100 mg tablets three times a day led to no improvement. She was subsequently diagnosed with smoldering multiple myeloma given 30% plasma cells in bone marrow which were Kappa and CD138 positive and after drop in hemoglobin and platelet was placed on daratumab regimen for IgA Kappa multiple myeloma.\u003c/p\u003e\n\u003cp\u003eOne year after the initial evaluation, she was evaluated in the emergency room with inability to ambulate, confusion, and urinary incontinence. As her platelets recovered to normal, lumbar puncture was performed, showing opening pressure of 60 cm H20, Protein \u0026gt;4,000 mg/dl (normal 15-45 mg/dl), but with negative CSF cytology. Pleural fluid cytology revealed plasma cells. She received further chemotherapy with return of normal mental status but remains with urinary incontinence and unable to ambulate.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eDiscussion\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003ePossible CNS involvement by myeloma was implied from worsening gait disturbance and elevated CSF protein. IgA myeloma is more likely to have CNS involvement but she doesn’t formally qualify for Bing Neely syndrome given absence of proof of plasma cells in the cerebrospinal fluid. It is possible that her neurological symptoms were due to blood brain barrier dysfunction.\u003c/p\u003e","manuscriptTitle":"Normal Pressure Hydrocephalus Exacerbation in Multiple Myeloma: Case Report","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-04-16 12:02:26","doi":"10.21203/rs.3.rs-6430094/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"73756a78-b3e4-4fac-b1e5-f4625bc80cdf","owner":[],"postedDate":"April 16th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[{"id":47183914,"name":"Oncology"}],"tags":[],"updatedAt":"2025-04-16T12:02:26+00:00","versionOfRecord":[],"versionCreatedAt":"2025-04-16 12:02:26","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-6430094","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-6430094","identity":"rs-6430094","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}