{"paper_id":"08c3c426-d965-4cb5-9e6f-0fc7922e7a20","body_text":"MRI-negative cerebellar syndrome caused by medication-induced magnesium deficiency: A 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 MRI-negative cerebellar syndrome caused by medication-induced magnesium deficiency: A case report Marvin Jüchtern This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-6998008/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 09 Sep, 2025 Read the published version in BMC Neurology → Version 1 posted 13 You are reading this latest preprint version Abstract Background Cerebellar pathologies in adults can have a wide range of hereditary, acquired and sporadic-degenerative causes. Due to the frequency in daily hospital, especially intensive care, settings, electrolyte imbalances are an important, yet rare differential diagnosis. The hypomagnesemia-induced cerebellar syndrome (HiCS) constitutes a relevant disease entity with clinical and morphological variability due to a potential progression of symptoms and a promising causal treatment. Cases of HiCS without imaging abnormalities are scarcely reported and pose a particular challenge to practitioners. Case presentation A 68-year-old female patient presented with subacute onset gait impairment and concomitant vertigo. Gaze induced nystagmus, ataxia and limb dysmetria became objectifiable. A broad diagnostic workup, including liquor puncture, whole-body positron emission tomography, antibody serology and most notably thin-layer magnetic resonance imaging remained unconclusive. Only a more detailed examination of chronic hypokalemia with the detection of severe magnesium deficiency under the intake of proton pump inhibitors and a recent gastrointestinal infection found a causal treatment through electrolyte substitution. Conclusions Electrolyte disorders as a reason for central nervous pathologies remain underdiagnosed and underestimated, as a heterogeneous clinical appearance, the growing number of defined cerebellar diseases and, like in our case, lacking imaging abnormality aggravatingly contrast with a high intake prevalence of triggering medication. The presence of diarrhea or vomiting, electrolyte shortage, cardiac arrhythmia, alcoholism and particularly the intake of proton pump inhibitors in patients with cerebellar symptoms should result in thorough electrolyte diagnostics. Hypomagnesemia cerebellar syndrome MRI proton pump inhibitors nystagmus Figures Figure 1 Background Coordination disturbance, central nystagmus and dysarthric articulation are indicative of a cerebellar pathology with a challenging diversity of possible differential diagnoses. Aside from an (ethyl)toxic, vascular, inflammatory, paraneoplastic and degenerative origin, also late-onset hereditary ataxias, infectious and metabolic causes come into consideration( 1 , 2 ). Increasing knowledge about – often drug-induced – electrolyte imbalances and their neuronal pathophysiology led to a greater awareness of in part rare manifestations of common laboratory aberrations. Although in neurology the focus is mostly on abnormalities of sodium (e.g. central pontine myelinolysis, symptomatic seizures) and potassium (e.g. episodic ataxia, periodic paralysis), magnesium plays a crucial role in ion channels, mitochondria and neuromuscular excitability( 3 ). Above all in intensive care settings, serious magnesium shortage is a relevant complication and associated with increased morbidity and mortality( 4 ). Beyond typical symptoms as carpopedal spasms, cardiac arrhythmia and bone instability, there are most notably central nervous manifestations of magnesium deficiency, including nystagmus, dizziness, epileptic seizures and confusion. The presented case shall illustrate the possibility of a hypomagnesemia-induced cerebellar syndrome (HiCS) with an absence of imaging abnormalities, its clinical variability, diagnostic considerations and therapeutic approach. Case presentation A 68-year-old woman presented with an exacerbation of gait instability over the course of nine days. The patient reported a staggering vertigo while sitting, standing and walking and described a lack of coordination of her left leg. She experienced nausea, daily emesis and diarrhea for two weeks before admission. Upon request, she reported a weight loss of 8 kg (17.64 lbs) in the last four months without the presence of fever or night sweats. Underlying medical conditions included arterial hypertension and gastroesophageal reflux. Alcohol consumption was explicitly denied. Long-term medication comprised antihypertensive, statin and proton pump inhibitor (PPI) therapy. The clinical examination revealed a horizontal gaze induced nystagmus with a vertical component, atactic pointing and pursuing tests of the upper and lower extremities with a left dominant intention tremor as well as a wide-based atactic gait pattern. The Romberg’s test was insecure with undirected tendency to fall. Vestibular testing remained unremarkable. There were no abnormalities in cranial computer tomography (CT). Laboratory examinations found a moderate hypokalemia (3.4 mmol/l) with normal sodium levels (142 mmol/l). Hypokalemia turned out to be recurring so that a continuous oral substitution was initiated. An investigation of the cerebrospinal fluid (CSF) remained unremarkable. We conducted a cranial magnetic resonance imaging (MRI) with thin-layered brainstem depiction and four-dimensional angiography that could not find aberrations of infratentorial brain structures even in a short-term follow-up. In particular, there were neither signs of vascular, inflammatory or tumorous lesions nor edema. A tumor screening by means of whole-body 18 fluorodeoxyglucose positron emission tomography (FDG-PET)/-CT, endoscopic examination and paraneoplastic serum antibodies remained negative. Further laboratory examinations revealed a severe magnesium-deficiency of 0.19 mmol/l (= 4.82 mg/l; reference value 0.66–0.99 mmol/l), in addition to therapy-resistant hypokalemia, which we initially interpreted in the context of a diagnosed Clostridioides difficile infection. Urinalysis solely found hypomagnesuria (< 1.18 mmol/24h). Through an assessment of previous laboratory findings, we could elicit a chronic magnesium and potassium deficiency due to long-term high-dose daily intake of omeprazole. A therapeutic attempt with intravenous methylprednisolone had been temporarily initiated without satisfactory effects. After detection of serum magnesium deficiency, we discontinued the PPI and began an intravenous substitution of magnesiumsulfate which was shifted to an oral maintenance treatment upon normalized blood levels of magnesium (0.64 mmol/l). Under this medication there was a rapid amelioration of cerebellar symptoms, with the patient being able to walk medium distances on her own. There was still evidence of a mild intention tremor on the left and a residual horizontal gaze-evoked nystagmus. In a follow-up visit eight months later, the patient reported only a mild constant gait imbalance; gastrointestinal symptoms, vertigo and nausea ceased permanently. Magnesium substitution and physiotherapy were regularly continued. There were persistent borderline magnesium levels (0.61 mmol/l) due to renewed prescription of omeprazole, which required an increase of the oral magnesium dosage. Discussion and Conclusions In synopsis of findings, we diagnosed a subacute hypomagnesemia-induced cerebellar syndrome in our patient. Etiologically we found a long-term high-dose PPI intake, which can be a typical cause of chronic magnesium deficiency( 5 , 6 , 7 , 8 , 9 ), as well as an acute aggravation resulting from a gastrointestinal infection. First reports of a cerebellar pathology due to magnesium shortage appeared in the early 1980’s within the context of enteropathies( 10 ) as well as associated with the taking of cyclosporine( 11 ). Only in the past years, a renewed reception of the phenomenon took place, which was summarized in a review by Kamm and colleagues( 5 ): In line with our case, HiCS generally presents as a subacute progressive disease with vertigo, nausea, oculomotor deficits (especially downbeat nystagmus( 9 , 12 , 13 )) and gait imbalance. The average age of onset was 58 +/- 14 years. In laboratory testing, magnesium levels below 0.2 mmol/l with concomitant potassium shortage were recorded as well as PPI intake as the cause in twelve of 18 cases. For all reported patients, substitution therapy led to a significant improvement of symptoms, albeit – as in our case – nearly half of all patients had residual complaints. In contrast to our patient, there were seven cases who had epileptic seizures, periodic nystagmus was common and notably 14 cases presented with MRI aberrations. Thus, it’s remarkable that five cases, including ours, had no signs of, mostly bilateral, cerebellar edema, although presenting with significantly disabling symptoms. Described MRI findings, which are typically perceptible in T2- and diffusion-weighted sequences and sometimes recurrent despite treatment, are considered as potentially reversible( 5 , 6 ) and had been compared to the posterior reversible encephalopathy syndrome (PRES)( 5 , 14 ). In PRES there is a frequent appearance of T2- and diffusion-weighted (DW-) MRI-hyperintensities without contrast agent uptake, especially in the parieto-occipital cortex, as well as headache, neuropsychiatric impairments, disturbance of consciousness and epileptic seizures( 15 ). All of these were not seen in the current patient, so we consider HiCS a clinically and etiologically separate disease entity. Biochemical relations illustrate the (patho)physiological importance of magnesium for the nervous system. While in the periphery it plays a relevant role for neuromuscular excitability which explains symptoms as tetanies, fasciculations and cramps, magnesium-dependent functional disturbances of cell membranes and mitochondria lead to central nervous (CNS) manifestation (e.g., seizures, nystagmus, confusion, choreoathetosis)( 3 ). HiCS therefore represents a regional CNS variant of hypomagnesemia-related disease, clinically heterogenous and – like in our patient – possibly without an imaging correlate. Typical causes of magnesium deficiency (lower threshold approx. 0.5–0.66 mmol/l ≈ 12–16 mg/l) are related to gastrointestinal and renal malfunction. Renal causes include hereditary-endocrine diseases (e.g. Gitelman’s syndrome) and most commonly medication (diuretics, cisplatin, aminoglycosides, among others). Gastrointestinal malabsorptive and malnutritive etiologies include the here evinced association with PPI (H + /K + ATPase inhibitors), which reduce paracellular magnesium absorption and magnesium-affinity of enterocytes due to a decreased intraluminal pH value( 16 ). Other reasons for hypomagnesemia can be hyper(para)thyroidism, albumin deficiency and type 1 or 2 diabetes( 3 ). Aside from treatment of triggering factors, hypomagnesemia therapy primarily builds upon substitution. Especially in cases of severe and rapidly evolving shortage and/or malabsorptive causes, an initial treatment with intravenous magnesium, e.g., 2g magnesiumsulfate and thereupon 4-6g (depending on kidney function) per day for three to five days( 3 ) appears appropriate. It should be followed by an oral long-term therapy, e.g., with 250-400mg two times a day or weight-adapted. Side effects of substitution can be nausea, vomiting and diarrhea; intoxication is possible and presents with hypotonia, muscle weakness, cardiac arrhythmia and – in severe cases – disturbance of consciousness( 17 ). In conclusion, hypomagnesemia represents an underestimated, yet clinically relevant cause of cerebellar symptoms, even if no imaging aberrations can be found. Thus, the following anamnestic, laboratory and clinical findings should remind of HiCS: A subacute cerebellar syndrome with or without epileptic seizures, diarrhea/emesis, cardiac arrhythmia, hypokalemia, intake of proton pump inhibitors or diuretics, diets and gastrointestinal malabsorption and alcoholism. A diagnostic workup should be parallelly conducted to a standard, syndrome-specific investigation and should comprise electrolyte analysis, thyroid and parathormone diagnostics, diabetes parameters, carbohydrate-deficient transferrin (CDT), vitamin levels, liver values and urinalysis. A follow-up of FLAIR and DW-MRI should be considered since morphological signs of HiCS can be transient. Treating physicians ought to discontinue potentially causal medication and initiate magnesium substitution as early as possible to avoid frequent symptomatic progression. Abbreviations MRI – Magnetic resonance imaging HiCS – Hypomagnesiemia-induced cerebellar syndrome PPI - Proton pump inhibitor CT – Computer tomography CRP – C-reactive protein CSF – Cerebrospinal fluid FDG-PET – 18 Fluorodeoxyglucose positron emission tomography FLAIR - Fluid-attenuated inversion recovery PRES - Posterior reversible encephalopathy syndrome DW – Diffusion-weighted (MRI) CNS – Central nervous system CDT - Carbohydrate-deficient transferrin Declarations Ethics approval and consent to participate For the retrospective data analysis, no ethics approval was required by the ethics committee of the RWTH Aachen University. The patient gave her consent to participate in written form. Consent for publication The patient gave written informed consent for their personal or clinical details along with any identifying images to be published in this study. Availability of data and material MRI data generated during this study are included in the published article. All datasets used during the current study are available from the corresponding author on reasonable request. Competing interests The author declares that there are no competing interests. Funding Not applicable. Authors’ contributions MJ was the treating physician, analyzed the patient data and wrote the manuscript. Acknowledgements I want to thank Dr. M. Mull for kindly providing and editing the shown imaging material as well as Dr. J. Pinho for revising the manuscript. References Klockgether Tea. Ataxien des Erwachsenenalters, S1-Leitlinie2018. Klockgether T. Sporadic ataxia with adult onset: classification and diagnostic criteria. Lancet Neurol. 2010;9(1):94-104. Martin KJ, Gonzalez EA, Slatopolsky E. Clinical consequences and management of hypomagnesemia. J Am Soc Nephrol. 2009;20(11):2291-5. Upala S, Jaruvongvanich V, Wijarnpreecha K, Sanguankeo A. Hypomagnesemia and mortality in patients admitted to intensive care unit: a systematic review and meta-analysis. QJM. 2016;109(7):453-9. Kamm CP, Nyffeler T, Henzen C, Fischli S. Hypomagnesemia-Induced Cerebellar Syndrome-A Distinct Disease Entity? Case Report and Literature Review. Front Neurol. 2020;11:968. Andrea R, Vittorio M, Giuseppe L, Paola B, Andrea S. Reversible cerebellar MRI hyperintensities and ataxia associated with hypomagnesemia: a case report with review of the literature. Neurol Sci. 2020;41(4):961-3. Bhana A, Waters MJ, Fazal MW, Kimber T. Pantoprazole-induced hypomagnesaemia causing cerebellar syndrome and seizures. Intern Med J. 2017;47(4):467-8. Fatuzzo P, Portale G, Scollo V, Zanoli L, Granata A. Proton pump inhibitors and symptomatic hypomagnesemic hypoparathyroidism. J Nephrol. 2017;30(2):297-301. Collia Fernandez A, Huete Anton B, Garcia-Monco JC. Progressive Ataxia and Downbeat Nystagmus in an Adult. JAMA Neurol. 2021;78(8):1018-9. Saul RF, Selhorst JB. Downbeat nystagmus with magnesium depletion. Arch Neurol. 1981;38(10):650-2. Thompson CB, June CH, Sullivan KM, Thomas ED. Association between cyclosporin neurotoxicity and hypomagnesaemia. Lancet. 1984;2(8412):1116-20. Viola P, Marcelli V, Sculco D, Pisani D, Caglioti A, Ricciardiello F, et al. Vestibular Disorders after Kidney Transplantation: Focus on the Pathophysiological Mechanisms Underlying the Vertical Nystagmus Associated with Tacrolimus-Related Hypomagnesamia. Int J Environ Res Public Health. 2022;19(4). Paramasivan NK, Yallapalli MK, Sundaram S, Vijayaraghavan A, Sukumaran S. Hypomagnesemia-induced encephalopathy with transient torsional nystagmus evolving into downbeat nystagmus: a rare complication of ileostomy. Acta Neurol Belg. 2022. Te Riele MG, Verrips A. Severe hypomagnesaemia causing reversible cerebellopathy. Cerebellum. 2014;13(5):659-62. Hinduja A. Posterior Reversible Encephalopathy Syndrome: Clinical Features and Outcome. Front Neurol. 2020;11:71. Perazella MA. Proton pump inhibitors and hypomagnesemia: a rare but serious complication. Kidney Int. 2013;83(4):553-6. Grober U, Schmidt J, Kisters K. Magnesium in Prevention and Therapy. Nutrients. 2015;7(9):8199-226. Additional Declarations No competing interests reported. Cite Share Download PDF Status: Published Journal Publication published 09 Sep, 2025 Read the published version in BMC Neurology → Version 1 posted Editorial decision: Revision requested 04 Aug, 2025 Reviews received at journal 03 Aug, 2025 Reviews received at journal 01 Aug, 2025 Reviews received at journal 31 Jul, 2025 Reviewers agreed at journal 26 Jul, 2025 Reviewers agreed at journal 25 Jul, 2025 Reviewers agreed at journal 24 Jul, 2025 Reviewers agreed at journal 24 Jul, 2025 Reviewers invited by journal 24 Jul, 2025 Editor assigned by journal 23 Jul, 2025 Editor invited by journal 03 Jul, 2025 Submission checks completed at journal 03 Jul, 2025 First submitted to journal 03 Jul, 2025 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. 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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-6998008\",\"acceptedTermsAndConditions\":true,\"allowDirectSubmit\":false,\"archivedVersions\":[],\"articleType\":\"Case Report\",\"associatedPublications\":[],\"authors\":[{\"id\":491326584,\"identity\":\"39b57ad9-bdc5-4962-8092-ecd138e05190\",\"order_by\":0,\"name\":\"Marvin Jüchtern\",\"email\":\"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA/0lEQVRIiWNgGAWjYLCCBAYGZiDFBubwg0k2YrUcAJKSDcRogQKIFoMDBLTotp99JvFwBwO7wfHmZ48/VNzLMz6/Ok2CocwGpxazM+lmEolnGJgNzhwzNzhwprjY7MbbzQYM59JwazmQxmyQ2Paf2eBGDpvEwbaExG03zm58wNh2GLeW889AWoC23H8D1PIvIXHzjLMbDjC2/cet5UYa4wOwlhs8QC0NCYkb+HtBthzAo+UZRIvkmTQziTPHEhJn3ODdbJBwLhmPw9IYDv5sY0jmO374mURFTUJif//ZbRIfyuxwaoEBJEMlEsCRSxAgGcp/gAj1o2AUjIJRMJIAAARwWrLt3UIqAAAAAElFTkSuQmCC\",\"orcid\":\"\",\"institution\":\"University Hospital, RWTH Aachen University\",\"correspondingAuthor\":true,\"prefix\":\"\",\"firstName\":\"Marvin\",\"middleName\":\"\",\"lastName\":\"Jüchtern\",\"suffix\":\"\"}],\"badges\":[],\"createdAt\":\"2025-06-28 13:08:19\",\"currentVersionCode\":1,\"declarations\":\"\",\"doi\":\"10.21203/rs.3.rs-6998008/v1\",\"doiUrl\":\"https://doi.org/10.21203/rs.3.rs-6998008/v1\",\"draftVersion\":[],\"editorialEvents\":[{\"content\":\"https://doi.org/10.1186/s12883-025-04399-8\",\"type\":\"published\",\"date\":\"2025-09-09T15:57:32+00:00\"}],\"editorialNote\":\"\",\"failedWorkflow\":false,\"files\":[{\"id\":87804574,\"identity\":\"e5aaf05b-cb23-49b8-afcc-1fd0fff97336\",\"added_by\":\"auto\",\"created_at\":\"2025-07-29 08:18:31\",\"extension\":\"png\",\"order_by\":1,\"title\":\"Figure 1\",\"display\":\"\",\"copyAsset\":false,\"role\":\"figure\",\"size\":350827,\"visible\":true,\"origin\":\"\",\"legend\":\"\\u003cp\\u003e\\u003cstrong\\u003eMRI of the patient’s neurocranium.\\u003c/strong\\u003e\\u003c/p\\u003e\\n\\u003cp\\u003eAxial FLAIR- (a) and sagittal T2 (b) sequences of thin-layered MRI with normal presentation of infratentorial brain structures. FLAIR = fluid-attenuated inversion recovery.\\u003c/p\\u003e\",\"description\":\"\",\"filename\":\"floatimage1.png\",\"url\":\"https://assets-eu.researchsquare.com/files/rs-6998008/v1/de08ae2dba032d0ce5c76d88.png\"},{\"id\":91359171,\"identity\":\"f9acae23-fe36-4a3d-9555-63e8d2b575f9\",\"added_by\":\"auto\",\"created_at\":\"2025-09-15 16:05:25\",\"extension\":\"pdf\",\"order_by\":0,\"title\":\"\",\"display\":\"\",\"copyAsset\":false,\"role\":\"manuscript-pdf\",\"size\":706007,\"visible\":true,\"origin\":\"\",\"legend\":\"\",\"description\":\"\",\"filename\":\"manuscript.pdf\",\"url\":\"https://assets-eu.researchsquare.com/files/rs-6998008/v1/0cc255b8-646d-4f5e-b126-0f3355e298e4.pdf\"}],\"financialInterests\":\"No competing interests reported.\",\"formattedTitle\":\"MRI-negative cerebellar syndrome caused by medication-induced magnesium deficiency: A case report\",\"fulltext\":[{\"header\":\"Background\",\"content\":\"\\u003cp\\u003eCoordination disturbance, central nystagmus and dysarthric articulation are indicative of a cerebellar pathology with a challenging diversity of possible differential diagnoses. Aside from an (ethyl)toxic, vascular, inflammatory, paraneoplastic and degenerative origin, also late-onset hereditary ataxias, infectious and metabolic causes come into consideration(\\u003cspan citationid=\\\"CR1\\\" class=\\\"CitationRef\\\"\\u003e1\\u003c/span\\u003e, \\u003cspan citationid=\\\"CR2\\\" class=\\\"CitationRef\\\"\\u003e2\\u003c/span\\u003e). Increasing knowledge about – often drug-induced – electrolyte imbalances and their neuronal pathophysiology led to a greater awareness of in part rare manifestations of common laboratory aberrations. Although in neurology the focus is mostly on abnormalities of sodium (e.g. central pontine myelinolysis, symptomatic seizures) and potassium (e.g. episodic ataxia, periodic paralysis), magnesium plays a crucial role in ion channels, mitochondria and neuromuscular excitability(\\u003cspan citationid=\\\"CR3\\\" class=\\\"CitationRef\\\"\\u003e3\\u003c/span\\u003e). Above all in intensive care settings, serious magnesium shortage is a relevant complication and associated with increased morbidity and mortality(\\u003cspan citationid=\\\"CR4\\\" class=\\\"CitationRef\\\"\\u003e4\\u003c/span\\u003e). Beyond typical symptoms as carpopedal spasms, cardiac arrhythmia and bone instability, there are most notably central nervous manifestations of magnesium deficiency, including nystagmus, dizziness, epileptic seizures and confusion. The presented case shall illustrate the possibility of a hypomagnesemia-induced cerebellar syndrome (HiCS) with an absence of imaging abnormalities, its clinical variability, diagnostic considerations and therapeutic approach.\\u003c/p\\u003e\"},{\"header\":\"Case presentation\",\"content\":\"\\u003cp\\u003eA 68-year-old woman presented with an exacerbation of gait instability over the course of nine days. The patient reported a staggering vertigo while sitting, standing and walking and described a lack of coordination of her left leg. She experienced nausea, daily emesis and diarrhea for two weeks before admission. Upon request, she reported a weight loss of 8 kg (17.64 lbs) in the last four months without the presence of fever or night sweats.\\u003c/p\\u003e\\u003cp\\u003eUnderlying medical conditions included arterial hypertension and gastroesophageal reflux. Alcohol consumption was explicitly denied. Long-term medication comprised antihypertensive, statin and proton pump inhibitor (PPI) therapy.\\u003c/p\\u003e\\u003cp\\u003eThe clinical examination revealed a horizontal gaze induced nystagmus with a vertical component, atactic pointing and pursuing tests of the upper and lower extremities with a left dominant intention tremor as well as a wide-based atactic gait pattern. The Romberg’s test was insecure with undirected tendency to fall. Vestibular testing remained unremarkable.\\u003c/p\\u003e\\u003cp\\u003eThere were no abnormalities in cranial computer tomography (CT). Laboratory examinations found a moderate hypokalemia (3.4 mmol/l) with normal sodium levels (142 mmol/l). Hypokalemia turned out to be recurring so that a continuous oral substitution was initiated. An investigation of the cerebrospinal fluid (CSF) remained unremarkable.\\u003c/p\\u003e\\u003cp\\u003eWe conducted a cranial magnetic resonance imaging (MRI) with thin-layered brainstem depiction and four-dimensional angiography that could not find aberrations of infratentorial brain structures even in a short-term follow-up. In particular, there were neither signs of vascular, inflammatory or tumorous lesions nor edema.\\u003c/p\\u003e\\u003cp\\u003eA tumor screening by means of whole-body \\u003csup\\u003e18\\u003c/sup\\u003efluorodeoxyglucose positron emission tomography (FDG-PET)/-CT, endoscopic examination and paraneoplastic serum antibodies remained negative.\\u003c/p\\u003e\\u003cp\\u003eFurther laboratory examinations revealed a severe magnesium-deficiency of 0.19 mmol/l (= 4.82 mg/l; reference value 0.66–0.99 mmol/l), in addition to therapy-resistant hypokalemia, which we initially interpreted in the context of a diagnosed Clostridioides difficile infection. Urinalysis solely found hypomagnesuria (\\u0026lt; 1.18 mmol/24h). Through an assessment of previous laboratory findings, we could elicit a chronic magnesium and potassium deficiency due to long-term high-dose daily intake of omeprazole.\\u003c/p\\u003e\\u003cp\\u003eA therapeutic attempt with intravenous methylprednisolone had been temporarily initiated without satisfactory effects.\\u003c/p\\u003e\\u003cp\\u003eAfter detection of serum magnesium deficiency, we discontinued the PPI and began an intravenous substitution of magnesiumsulfate which was shifted to an oral maintenance treatment upon normalized blood levels of magnesium (0.64 mmol/l). Under this medication there was a rapid amelioration of cerebellar symptoms, with the patient being able to walk medium distances on her own. There was still evidence of a mild intention tremor on the left and a residual horizontal gaze-evoked nystagmus.\\u003c/p\\u003e\\u003cp\\u003eIn a follow-up visit eight months later, the patient reported only a mild constant gait imbalance; gastrointestinal symptoms, vertigo and nausea ceased permanently. Magnesium substitution and physiotherapy were regularly continued. There were persistent borderline magnesium levels (0.61 mmol/l) due to renewed prescription of omeprazole, which required an increase of the oral magnesium dosage.\\u003c/p\\u003e\"},{\"header\":\"Discussion and Conclusions\",\"content\":\"\\u003cp\\u003eIn synopsis of findings, we diagnosed a subacute hypomagnesemia-induced cerebellar syndrome in our patient. Etiologically we found a long-term high-dose PPI intake, which can be a typical cause of chronic magnesium deficiency(\\u003cspan citationid=\\\"CR5\\\" class=\\\"CitationRef\\\"\\u003e5\\u003c/span\\u003e, \\u003cspan citationid=\\\"CR6\\\" class=\\\"CitationRef\\\"\\u003e6\\u003c/span\\u003e, \\u003cspan citationid=\\\"CR7\\\" class=\\\"CitationRef\\\"\\u003e7\\u003c/span\\u003e, \\u003cspan citationid=\\\"CR8\\\" class=\\\"CitationRef\\\"\\u003e8\\u003c/span\\u003e, \\u003cspan citationid=\\\"CR9\\\" class=\\\"CitationRef\\\"\\u003e9\\u003c/span\\u003e), as well as an acute aggravation resulting from a gastrointestinal infection.\\u003c/p\\u003e\\u003cp\\u003eFirst reports of a cerebellar pathology due to magnesium shortage appeared in the early 1980’s within the context of enteropathies(\\u003cspan citationid=\\\"CR10\\\" class=\\\"CitationRef\\\"\\u003e10\\u003c/span\\u003e) as well as associated with the taking of cyclosporine(\\u003cspan citationid=\\\"CR11\\\" class=\\\"CitationRef\\\"\\u003e11\\u003c/span\\u003e). Only in the past years, a renewed reception of the phenomenon took place, which was summarized in a review by Kamm and colleagues(\\u003cspan citationid=\\\"CR5\\\" class=\\\"CitationRef\\\"\\u003e5\\u003c/span\\u003e): In line with our case, HiCS generally presents as a subacute progressive disease with vertigo, nausea, oculomotor deficits (especially downbeat nystagmus(\\u003cspan citationid=\\\"CR9\\\" class=\\\"CitationRef\\\"\\u003e9\\u003c/span\\u003e, \\u003cspan citationid=\\\"CR12\\\" class=\\\"CitationRef\\\"\\u003e12\\u003c/span\\u003e, \\u003cspan citationid=\\\"CR13\\\" class=\\\"CitationRef\\\"\\u003e13\\u003c/span\\u003e)) and gait imbalance. The average age of onset was 58 +/- 14 years. In laboratory testing, magnesium levels below 0.2 mmol/l with concomitant potassium shortage were recorded as well as PPI intake as the cause in twelve of 18 cases. For all reported patients, substitution therapy led to a significant improvement of symptoms, albeit – as in our case – nearly half of all patients had residual complaints. In contrast to our patient, there were seven cases who had epileptic seizures, periodic nystagmus was common and notably 14 cases presented with MRI aberrations.\\u003c/p\\u003e\\u003cp\\u003eThus, it’s remarkable that five cases, including ours, had no signs of, mostly bilateral, cerebellar edema, although presenting with significantly disabling symptoms. Described MRI findings, which are typically perceptible in T2- and diffusion-weighted sequences and sometimes recurrent despite treatment, are considered as potentially reversible(\\u003cspan citationid=\\\"CR5\\\" class=\\\"CitationRef\\\"\\u003e5\\u003c/span\\u003e, \\u003cspan citationid=\\\"CR6\\\" class=\\\"CitationRef\\\"\\u003e6\\u003c/span\\u003e) and had been compared to the posterior reversible encephalopathy syndrome (PRES)(\\u003cspan citationid=\\\"CR5\\\" class=\\\"CitationRef\\\"\\u003e5\\u003c/span\\u003e, \\u003cspan citationid=\\\"CR14\\\" class=\\\"CitationRef\\\"\\u003e14\\u003c/span\\u003e). In PRES there is a frequent appearance of T2- and diffusion-weighted (DW-) MRI-hyperintensities without contrast agent uptake, especially in the parieto-occipital cortex, as well as headache, neuropsychiatric impairments, disturbance of consciousness and epileptic seizures(\\u003cspan citationid=\\\"CR15\\\" class=\\\"CitationRef\\\"\\u003e15\\u003c/span\\u003e). All of these were not seen in the current patient, so we consider HiCS a clinically and etiologically separate disease entity.\\u003c/p\\u003e\\u003cp\\u003eBiochemical relations illustrate the (patho)physiological importance of magnesium for the nervous system. While in the periphery it plays a relevant role for neuromuscular excitability which explains symptoms as tetanies, fasciculations and cramps, magnesium-dependent functional disturbances of cell membranes and mitochondria lead to central nervous (CNS) manifestation (e.g., seizures, nystagmus, confusion, choreoathetosis)(\\u003cspan citationid=\\\"CR3\\\" class=\\\"CitationRef\\\"\\u003e3\\u003c/span\\u003e). HiCS therefore represents a regional CNS variant of hypomagnesemia-related disease, clinically heterogenous and – like in our patient – possibly without an imaging correlate.\\u003c/p\\u003e\\u003cp\\u003eTypical causes of magnesium deficiency (lower threshold approx. 0.5–0.66 mmol/l ≈ 12–16 mg/l) are related to gastrointestinal and renal malfunction. Renal causes include hereditary-endocrine diseases (e.g. Gitelman’s syndrome) and most commonly medication (diuretics, cisplatin, aminoglycosides, among others). Gastrointestinal malabsorptive and malnutritive etiologies include the here evinced association with PPI (H\\u003csup\\u003e+\\u003c/sup\\u003e/K\\u003csup\\u003e+\\u003c/sup\\u003e ATPase inhibitors), which reduce paracellular magnesium absorption and magnesium-affinity of enterocytes due to a decreased intraluminal pH value(\\u003cspan citationid=\\\"CR16\\\" class=\\\"CitationRef\\\"\\u003e16\\u003c/span\\u003e). Other reasons for hypomagnesemia can be hyper(para)thyroidism, albumin deficiency and type 1 or 2 diabetes(\\u003cspan citationid=\\\"CR3\\\" class=\\\"CitationRef\\\"\\u003e3\\u003c/span\\u003e).\\u003c/p\\u003e\\u003cp\\u003eAside from treatment of triggering factors, hypomagnesemia therapy primarily builds upon substitution. Especially in cases of severe and rapidly evolving shortage and/or malabsorptive causes, an initial treatment with intravenous magnesium, e.g., 2g magnesiumsulfate and thereupon 4-6g (depending on kidney function) per day for three to five days(\\u003cspan citationid=\\\"CR3\\\" class=\\\"CitationRef\\\"\\u003e3\\u003c/span\\u003e) appears appropriate. It should be followed by an oral long-term therapy, e.g., with 250-400mg two times a day or weight-adapted. Side effects of substitution can be nausea, vomiting and diarrhea; intoxication is possible and presents with hypotonia, muscle weakness, cardiac arrhythmia and – in severe cases – disturbance of consciousness(\\u003cspan citationid=\\\"CR17\\\" class=\\\"CitationRef\\\"\\u003e17\\u003c/span\\u003e).\\u003c/p\\u003e\\u003cp\\u003eIn conclusion, hypomagnesemia represents an underestimated, yet clinically relevant cause of cerebellar symptoms, even if no imaging aberrations can be found. Thus, the following anamnestic, laboratory and clinical findings should remind of HiCS: A subacute cerebellar syndrome with or without epileptic seizures, diarrhea/emesis, cardiac arrhythmia, hypokalemia, intake of proton pump inhibitors or diuretics, diets and gastrointestinal malabsorption and alcoholism. A diagnostic workup should be parallelly conducted to a standard, syndrome-specific investigation and should comprise electrolyte analysis, thyroid and parathormone diagnostics, diabetes parameters, carbohydrate-deficient transferrin (CDT), vitamin levels, liver values and urinalysis. A follow-up of FLAIR and DW-MRI should be considered since morphological signs of HiCS can be transient. Treating physicians ought to discontinue potentially causal medication and initiate magnesium substitution as early as possible to avoid frequent symptomatic progression.\\u003c/p\\u003e\"},{\"header\":\"Abbreviations\",\"content\":\"\\u003cp\\u003eMRI \\u0026ndash; Magnetic resonance imaging\\u003c/p\\u003e\\n\\u003cp\\u003eHiCS \\u0026ndash; Hypomagnesiemia-induced cerebellar syndrome\\u003c/p\\u003e\\n\\u003cp\\u003ePPI - Proton pump inhibitor\\u003c/p\\u003e\\n\\u003cp\\u003eCT \\u0026ndash; Computer tomography\\u003c/p\\u003e\\n\\u003cp\\u003eCRP \\u0026ndash; C-reactive protein\\u003c/p\\u003e\\n\\u003cp\\u003eCSF \\u0026ndash; Cerebrospinal fluid\\u003c/p\\u003e\\n\\u003cp\\u003eFDG-PET \\u0026ndash; \\u003csup\\u003e18\\u003c/sup\\u003eFluorodeoxyglucose positron emission tomography\\u003c/p\\u003e\\n\\u003cp\\u003eFLAIR - Fluid-attenuated inversion recovery\\u003c/p\\u003e\\n\\u003cp\\u003ePRES - Posterior reversible encephalopathy syndrome\\u003c/p\\u003e\\n\\u003cp\\u003eDW \\u0026ndash; Diffusion-weighted (MRI)\\u003c/p\\u003e\\n\\u003cp\\u003eCNS \\u0026ndash; Central nervous system\\u003c/p\\u003e\\n\\u003cp\\u003eCDT - Carbohydrate-deficient transferrin\\u003c/p\\u003e\"},{\"header\":\"Declarations\",\"content\":\"\\u003cp\\u003e\\u003cstrong\\u003eEthics approval and consent to participate\\u003c/strong\\u003e\\u003c/p\\u003e\\n\\u003cp\\u003eFor the retrospective data analysis, no ethics approval was required by the ethics committee of the RWTH Aachen University. The patient gave her consent to participate in written form.\\u003c/p\\u003e\\n\\u003cp\\u003e\\u003cstrong\\u003eConsent for publication\\u003c/strong\\u003e\\u003c/p\\u003e\\n\\u003cp\\u003eThe patient gave written informed consent for their personal or clinical details along with any identifying images to be published in this study.\\u003c/p\\u003e\\n\\u003cp\\u003e\\u003cstrong\\u003eAvailability of data and material\\u003c/strong\\u003e\\u003c/p\\u003e\\n\\u003cp\\u003eMRI data generated during this study are included in the published article.\\u003c/p\\u003e\\n\\u003cp\\u003eAll datasets used during the current study are available from the corresponding author on reasonable request.\\u003c/p\\u003e\\n\\u003cp\\u003e\\u003cstrong\\u003eCompeting interests\\u003c/strong\\u003e\\u003c/p\\u003e\\n\\u003cp\\u003eThe author declares that there are no competing interests.\\u003c/p\\u003e\\n\\u003cp\\u003e\\u003cstrong\\u003eFunding\\u003c/strong\\u003e\\u003c/p\\u003e\\n\\u003cp\\u003eNot applicable.\\u003c/p\\u003e\\n\\u003cp\\u003e\\u003cstrong\\u003eAuthors\\u0026rsquo; contributions\\u003c/strong\\u003e\\u003c/p\\u003e\\n\\u003cp\\u003eMJ was the treating physician, analyzed the patient data and wrote the manuscript.\\u003c/p\\u003e\\n\\u003cp\\u003e\\u003cstrong\\u003eAcknowledgements\\u003c/strong\\u003e\\u003c/p\\u003e\\n\\u003cp\\u003eI want to thank Dr. M. Mull for kindly providing and editing the shown imaging material as well as Dr. J. Pinho for revising the manuscript.\\u003c/p\\u003e\"},{\"header\":\"References\",\"content\":\"\\u003col\\u003e\\n\\u003cli\\u003eKlockgether Tea. Ataxien des Erwachsenenalters, S1-Leitlinie2018.\\u003c/li\\u003e\\n\\u003cli\\u003eKlockgether T. Sporadic ataxia with adult onset: classification and diagnostic criteria. Lancet Neurol. 2010;9(1):94-104.\\u003c/li\\u003e\\n\\u003cli\\u003eMartin KJ, Gonzalez EA, Slatopolsky E. Clinical consequences and management of hypomagnesemia. J Am Soc Nephrol. 2009;20(11):2291-5.\\u003c/li\\u003e\\n\\u003cli\\u003eUpala S, Jaruvongvanich V, Wijarnpreecha K, Sanguankeo A. Hypomagnesemia and mortality in patients admitted to intensive care unit: a systematic review and meta-analysis. QJM. 2016;109(7):453-9.\\u003c/li\\u003e\\n\\u003cli\\u003eKamm CP, Nyffeler T, Henzen C, Fischli S. Hypomagnesemia-Induced Cerebellar Syndrome-A Distinct Disease Entity? Case Report and Literature Review. Front Neurol. 2020;11:968.\\u003c/li\\u003e\\n\\u003cli\\u003eAndrea R, Vittorio M, Giuseppe L, Paola B, Andrea S. Reversible cerebellar MRI hyperintensities and ataxia associated with hypomagnesemia: a case report with review of the literature. Neurol Sci. 2020;41(4):961-3.\\u003c/li\\u003e\\n\\u003cli\\u003eBhana A, Waters MJ, Fazal MW, Kimber T. Pantoprazole-induced hypomagnesaemia causing cerebellar syndrome and seizures. Intern Med J. 2017;47(4):467-8.\\u003c/li\\u003e\\n\\u003cli\\u003eFatuzzo P, Portale G, Scollo V, Zanoli L, Granata A. Proton pump inhibitors and symptomatic hypomagnesemic hypoparathyroidism. J Nephrol. 2017;30(2):297-301.\\u003c/li\\u003e\\n\\u003cli\\u003eCollia Fernandez A, Huete Anton B, Garcia-Monco JC. Progressive Ataxia and Downbeat Nystagmus in an Adult. JAMA Neurol. 2021;78(8):1018-9.\\u003c/li\\u003e\\n\\u003cli\\u003eSaul RF, Selhorst JB. Downbeat nystagmus with magnesium depletion. Arch Neurol. 1981;38(10):650-2.\\u003c/li\\u003e\\n\\u003cli\\u003eThompson CB, June CH, Sullivan KM, Thomas ED. Association between cyclosporin neurotoxicity and hypomagnesaemia. Lancet. 1984;2(8412):1116-20.\\u003c/li\\u003e\\n\\u003cli\\u003eViola P, Marcelli V, Sculco D, Pisani D, Caglioti A, Ricciardiello F, et al. Vestibular Disorders after Kidney Transplantation: Focus on the Pathophysiological Mechanisms Underlying the Vertical Nystagmus Associated with Tacrolimus-Related Hypomagnesamia. Int J Environ Res Public Health. 2022;19(4).\\u003c/li\\u003e\\n\\u003cli\\u003eParamasivan NK, Yallapalli MK, Sundaram S, Vijayaraghavan A, Sukumaran S. Hypomagnesemia-induced encephalopathy with transient torsional nystagmus evolving into downbeat nystagmus: a rare complication of ileostomy. Acta Neurol Belg. 2022.\\u003c/li\\u003e\\n\\u003cli\\u003eTe Riele MG, Verrips A. Severe hypomagnesaemia causing reversible cerebellopathy. Cerebellum. 2014;13(5):659-62.\\u003c/li\\u003e\\n\\u003cli\\u003eHinduja A. Posterior Reversible Encephalopathy Syndrome: Clinical Features and Outcome. Front Neurol. 2020;11:71.\\u003c/li\\u003e\\n\\u003cli\\u003ePerazella MA. Proton pump inhibitors and hypomagnesemia: a rare but serious complication. Kidney Int. 2013;83(4):553-6.\\u003c/li\\u003e\\n\\u003cli\\u003eGrober U, Schmidt J, Kisters K. Magnesium in Prevention and Therapy. Nutrients. 2015;7(9):8199-226.\\u003c/li\\u003e\\n\\u003c/ol\\u003e\"}],\"fulltextSource\":\"\",\"fullText\":\"\",\"funders\":[],\"hasAdminPriorityOnWorkflow\":false,\"hasManuscriptDocX\":true,\"hasOptedInToPreprint\":true,\"hasPassedJournalQc\":\"\",\"hasAnyPriority\":false,\"hideJournal\":false,\"highlight\":\"\",\"institution\":\"\",\"isAcceptedByJournal\":true,\"isAuthorSuppliedPdf\":false,\"isDeskRejected\":\"\",\"isHiddenFromSearch\":false,\"isInQc\":false,\"isInWorkflow\":false,\"isPdf\":false,\"isPdfUpToDate\":true,\"isWithdrawnOrRetracted\":false,\"journal\":{\"display\":true,\"email\":\"info@researchsquare.com\",\"identity\":\"bmc-neurology\",\"isNatureJournal\":false,\"hasQc\":true,\"allowDirectSubmit\":false,\"externalIdentity\":\"nurl\",\"sideBox\":\"Learn more about [BMC Neurology](http://bmcneurol.biomedcentral.com/)\",\"snPcode\":\"\",\"submissionUrl\":\"https://www.editorialmanager.com/nurl\",\"title\":\"BMC Neurology\",\"twitterHandle\":\"BMC_series\",\"acdcEnabled\":true,\"dfaEnabled\":false,\"editorialSystem\":\"em\",\"reportingPortfolio\":\"BMC Series\",\"inReviewEnabled\":true,\"inReviewRevisionsEnabled\":true},\"keywords\":\"Hypomagnesemia, cerebellar syndrome, MRI, proton pump inhibitors, nystagmus\",\"lastPublishedDoi\":\"10.21203/rs.3.rs-6998008/v1\",\"lastPublishedDoiUrl\":\"https://doi.org/10.21203/rs.3.rs-6998008/v1\",\"license\":{\"name\":\"CC BY 4.0\",\"url\":\"https://creativecommons.org/licenses/by/4.0/\"},\"manuscriptAbstract\":\"\\u003cp\\u003eBackground\\u003c/p\\u003e\\n\\u003cp\\u003eCerebellar pathologies in adults can have a wide range of hereditary, acquired and sporadic-degenerative causes. Due to the frequency in daily hospital, especially intensive care, settings, electrolyte imbalances are an important, yet rare differential diagnosis. The hypomagnesemia-induced cerebellar syndrome (HiCS) constitutes a relevant disease entity with clinical and morphological variability due to a potential progression of symptoms and a promising causal treatment. Cases of HiCS without imaging abnormalities are scarcely reported and pose a particular challenge to practitioners.\\u003c/p\\u003e\\n\\u003cp\\u003eCase presentation\\u003c/p\\u003e\\n\\u003cp\\u003eA 68-year-old female patient presented with subacute onset gait impairment and concomitant vertigo. Gaze induced nystagmus, ataxia and limb dysmetria became objectifiable. A broad diagnostic workup, including liquor puncture, whole-body positron emission tomography, antibody serology and most notably thin-layer magnetic resonance imaging remained unconclusive. Only a more detailed examination of chronic hypokalemia with the detection of severe magnesium deficiency under the intake of proton pump inhibitors and a recent gastrointestinal infection found a causal treatment through electrolyte substitution.\\u003c/p\\u003e\\n\\u003cp\\u003eConclusions\\u003c/p\\u003e\\n\\u003cp\\u003eElectrolyte disorders as a reason for central nervous pathologies remain underdiagnosed and underestimated, as a heterogeneous clinical appearance, the growing number of defined cerebellar diseases and, like in our case, lacking imaging abnormality aggravatingly contrast with a high intake prevalence of triggering medication. The presence of diarrhea or vomiting, electrolyte shortage, cardiac arrhythmia, alcoholism and particularly the intake of proton pump inhibitors in patients with cerebellar symptoms should result in thorough electrolyte diagnostics.\\u003c/p\\u003e\",\"manuscriptTitle\":\"MRI-negative cerebellar syndrome caused by medication-induced magnesium deficiency: A case report\",\"msid\":\"\",\"msnumber\":\"\",\"nonDraftVersions\":[{\"code\":1,\"date\":\"2025-07-29 08:18:27\",\"doi\":\"10.21203/rs.3.rs-6998008/v1\",\"editorialEvents\":[{\"type\":\"communityComments\",\"content\":0},{\"type\":\"decision\",\"content\":\"Revision requested\",\"date\":\"2025-08-04T15:52:34+00:00\",\"index\":\"\",\"fulltext\":\"\"},{\"type\":\"editorInvitedReview\",\"content\":\"\",\"date\":\"2025-08-03T09:12:25+00:00\",\"index\":\"hide\",\"fulltext\":\"\"},{\"type\":\"editorInvitedReview\",\"content\":\"\",\"date\":\"2025-08-01T15:35:53+00:00\",\"index\":\"hide\",\"fulltext\":\"\"},{\"type\":\"editorInvitedReview\",\"content\":\"\",\"date\":\"2025-07-31T16:41:52+00:00\",\"index\":\"hide\",\"fulltext\":\"\"},{\"type\":\"reviewerAgreed\",\"content\":\"16596289010035483986314882930276361029\",\"date\":\"2025-07-26T17:07:07+00:00\",\"index\":\"hide\",\"fulltext\":\"\"},{\"type\":\"reviewerAgreed\",\"content\":\"75593200869399584356604978047501431227\",\"date\":\"2025-07-25T13:37:03+00:00\",\"index\":\"hide\",\"fulltext\":\"\"},{\"type\":\"reviewerAgreed\",\"content\":\"136778310035392839877050747635582493025\",\"date\":\"2025-07-24T16:39:58+00:00\",\"index\":\"hide\",\"fulltext\":\"\"},{\"type\":\"reviewerAgreed\",\"content\":\"235955462556474301756108485699148401462\",\"date\":\"2025-07-24T16:26:10+00:00\",\"index\":\"hide\",\"fulltext\":\"\"},{\"type\":\"reviewersInvited\",\"content\":\"\",\"date\":\"2025-07-24T16:22:10+00:00\",\"index\":\"\",\"fulltext\":\"\"},{\"type\":\"editorAssigned\",\"content\":\"\",\"date\":\"2025-07-24T01:27:53+00:00\",\"index\":\"\",\"fulltext\":\"\"},{\"type\":\"editorInvited\",\"content\":\"\",\"date\":\"2025-07-03T17:39:16+00:00\",\"index\":\"\",\"fulltext\":\"\"},{\"type\":\"checksComplete\",\"content\":\"\",\"date\":\"2025-07-03T15:43:54+00:00\",\"index\":\"\",\"fulltext\":\"\"},{\"type\":\"submitted\",\"content\":\"BMC Neurology\",\"date\":\"2025-07-03T15:41:29+00:00\",\"index\":\"\",\"fulltext\":\"\"}],\"status\":\"published\",\"journal\":{\"display\":true,\"email\":\"info@researchsquare.com\",\"identity\":\"bmc-neurology\",\"isNatureJournal\":false,\"hasQc\":true,\"allowDirectSubmit\":false,\"externalIdentity\":\"nurl\",\"sideBox\":\"Learn more about [BMC Neurology](http://bmcneurol.biomedcentral.com/)\",\"snPcode\":\"\",\"submissionUrl\":\"https://www.editorialmanager.com/nurl\",\"title\":\"BMC Neurology\",\"twitterHandle\":\"BMC_series\",\"acdcEnabled\":true,\"dfaEnabled\":false,\"editorialSystem\":\"em\",\"reportingPortfolio\":\"BMC Series\",\"inReviewEnabled\":true,\"inReviewRevisionsEnabled\":true}}],\"origin\":\"\",\"ownerIdentity\":\"179306fc-4bbc-48bf-ad36-c3c86b90097e\",\"owner\":[],\"postedDate\":\"July 29th, 2025\",\"published\":true,\"recentEditorialEvents\":[],\"rejectedJournal\":[],\"revision\":\"\",\"amendment\":\"\",\"status\":\"published-in-journal\",\"subjectAreas\":[],\"tags\":[],\"updatedAt\":\"2025-09-15T16:04:20+00:00\",\"versionOfRecord\":{\"articleIdentity\":\"rs-6998008\",\"link\":\"https://doi.org/10.1186/s12883-025-04399-8\",\"journal\":{\"identity\":\"bmc-neurology\",\"isVorOnly\":false,\"title\":\"BMC Neurology\"},\"publishedOn\":\"2025-09-09 15:57:32\",\"publishedOnDateReadable\":\"September 9th, 2025\"},\"versionCreatedAt\":\"2025-07-29 08:18:27\",\"video\":\"\",\"vorDoi\":\"10.1186/s12883-025-04399-8\",\"vorDoiUrl\":\"https://doi.org/10.1186/s12883-025-04399-8\",\"workflowStages\":[]},\"version\":\"v1\",\"identity\":\"rs-6998008\",\"journalConfig\":\"researchsquare\"},\"__N_SSP\":true},\"page\":\"/article/[identity]/[[...version]]\",\"query\":{\"redirect\":\"/article/rs-6998008\",\"identity\":\"rs-6998008\",\"version\":[\"v1\"]},\"buildId\":\"XKTyCvWXoU3ODBz1xrDgd\",\"isFallback\":false,\"isExperimentalCompile\":false,\"dynamicIds\":[84888],\"gssp\":true,\"scriptLoader\":[]}","source_license":"CC-BY-4.0","license_restricted":false}