How often should we perform magnetic resonance imaging (MRI) for the follow-up of pituitary adenoma?

Magnetic resonance imaging (MRI) is the examination of choice for diagnosing and monitoring pituitary adenoma (also known as pituitary neuroendocrine tumor or PitNET), whether treated or not. However, repeating the examination too often (and sometimes unnecessarily) is costly, and worrying data on tissue accumulation (brain, bone, etc.) of gadolinium atoms dissociated from their carrier molecule (chelator) have led European authorities to ban contrast agents based on linear chelators of gadolinium, which are particularly susceptible to rapid dissociation, in favor of chemically more stable macrocyclic chelators. It is therefore important to determine the optimal frequency for pituitary MRI monitoring in order to safely assess the natural history or therapeutic response of pituitary adenomas. The aim of this article is to summarize the most recent data on optimal follow-up intervals depending on the type, size and location of the pituitary tumor and the clinical situation in general, in order to generate monitoring algorithms to guide clinicians.

Natural history and surgical outcome of incidentally discovered clinically nonfunctioning pituitary macroadenomas.

Objectives: The incidental diagnosis of nonfunctioning pituitary macroadenomas (NFPMAs) is becoming more prevalent with the spread of modern brain imaging techniques. We sought to uncover new data about their natural history and surgical outcome. Design: This is a retrospective single-center observational study. Methods: Among 210 patients seen for a NFPMA between 2010 and 2019, 70 (33%) were discovered incidentally (i-NFPMA). We analyzed outcomes in a total of 65 patients with available follow-up data. Results: Mean age at diagnosis (± s.d.) was 60 ± 14 years and mean maximal diameter was 20.0 ± 7.3 mm. At diagnosis, 29 patients (45%) had pituitary hormone deficits (LH/FSH 41%, TSH 29%, ACTH 15%) and 12% had visual field deficits. 26 patients underwent initial surgery, while 12 had delayed surgery after initial surveillance. In the surveillance group, the risk of tumor growth was estimated at 10%/year. Patients with hormonal deficits at diagnosis experienced earlier growth at 24 months (P < 0.02). Overall, surgical resection of the i-NFPMA led to stable or improved endocrine function in 91% of patients, with only 6% postoperative permanent diabetes insipidus. Moreover, surgery was more effective in preserving intact endocrine function (10/12) than restoring altered endocrine function to normal (6/22, P = 0.03). Conclusion: About one-third of NFPMAs are now discovered incidentally and a significant subset may be responsible for unrecognized endocrine and visual deficits. Under surveillance the risk of further tumor growth is significant (10%/year) and seems to occur faster in patients already harboring an endocrine deficit. Early surgical removal before onset of endocrine deficits appears to lead to better endocrine outcome.

Comparable Accuracy of Quantitative and Visual Analyses of [18F]FDG PET/CT for the Detection of Lymph Node Metastases from Head and Neck Squamous Cell Carcinoma.

BACKGROUND: In head and neck squamous cell carcinoma (HNSCC), [18F]FDG PET/CT is recommended for detecting recurrent disease and in the initial staging for evaluating distant metastases, but its use in detecting cervical lymph metastases remains unclear. The aim of this study is to evaluate and compare the diagnostic accuracy of [8F]FDG-PET/CT using visual and semi-quantitative analyses for detecting the nodal involvement in HNSCC. METHODS: We analyzed consecutive patients who underwent a preoperative [18F]FDG-PET/CT and neck dissection for HNSCC at our tertiary hospital. A blinded evaluation of the [18F]FDG uptake in each neck level was performed using a semi-quantitative approach (SUVmax and SUVR) and a visual grading system (uptake superior to the internal jugular vein for grade 1 and superior to the liver for grade 2). Analyses were compared to the histological results. RESULTS: In our 211 patients, analyses demonstrated similar diagnostic accuracy using a semi-quantitative approach or a visual grading system. Regarding the visual grading system, [18F]FDG-PET/CT detected nodal metastases with a specificity of 83% for lymph nodes classified as grade 1 and 98% for those classified as grade 2. The sensitivity was moderate, ranging from 60 to 63%. CONCLUSIONS: [18F]FDG PET/CT has a high specificity for detecting lymph node metastases in HNSCC and therefore must be considered in the nodal clinical staging.

B cell depletion therapy does not resolve chronic active multiple sclerosis lesions.

BACKGROUND: Chronic active lesions (CAL) in multiple sclerosis (MS) have been observed even in patients taking high-efficacy disease-modifying therapy, including B-cell depletion. Given that CAL are a major determinant of clinical progression, including progression independent of relapse activity (PIRA), understanding the predicted activity and real-world effects of targeting specific lymphocyte populations is critical for designing next-generation treatments to mitigate chronic inflammation in MS. METHODS: We analyzed published lymphocyte single-cell transcriptomes from MS lesions and bioinformatically predicted the effects of depleting lymphocyte subpopulations (including CD20 B-cells) from CAL via gene-regulatory-network machine-learning analysis. Motivated by the results, we performed in vivo MRI assessment of PRL changes in 72 adults with MS, 46 treated with anti-CD20 antibodies and 26 untreated, over ∼2 years. FINDINGS: Although only 4.3% of lymphocytes in CAL were CD20 B-cells, their depletion is predicted to affect microglial genes involved in iron/heme metabolism, hypoxia, and antigen presentation. In vivo, tracking 202 PRL (150 treated) and 175 non-PRL (124 treated), none of the treated paramagnetic rims disappeared at follow-up, nor was there a treatment effect on PRL for lesion volume, magnetic susceptibility, or T1 time. PIRA occurred in 20% of treated patients, more frequently in those with ≥4 PRL (p = 0.027). INTERPRETATION: Despite predicted effects on microglia-mediated inflammatory networks in CAL and iron metabolism, anti-CD20 therapies do not fully resolve PRL after 2-year MRI follow up. Limited tissue turnover of B-cells, inefficient passage of anti-CD20 antibodies across the blood-brain-barrier, and a paucity of B-cells in CAL could explain our findings. FUNDING: Intramural Research Program of NINDS, NIH; NINDS grants R01NS082347 and R01NS082347; Dr. Miriam and Sheldon G. Adelson Medical Research Foundation; Cariplo Foundation (grant #1677), FRRB Early Career Award (grant #1750327); Fund for Scientific Research (FNRS).

Cognitive trajectories in relapsing-remitting multiple sclerosis: Evidence of multiple evolutionary trends.

BACKGROUND: Cognitive impairment (CI) frequently occurs in multiple sclerosis (MS) and is assumed to increase over time. However, recent studies have suggested that the evolution of cognitive status in patients with MS may be more heterogeneous than expected. Predicting CI remains also challenging, and longitudinal studies exploring the baseline determinants of cognitive performances are limited. No studies have explored the predictive value of patient-reported outcome measures (PROMs) regarding future CI. OBJECTIVE: To explore the evolutionary patterns of cognitive status in a cohort of RRMS patients initiating a new disease modifying treatment (DMT), and to determine whether PROMs may have a predictive value for future CI. METHODS: The present prospective study is a 12-month follow-up of a cohort of 59 RRMS patients who underwent yearly a comprehensive, multiparametric assessment combining clinical (with EDSS assessment), neuropsychological (BVMT-R, SDMT, CVLT-II), MRI-derived metrics and a set of self-reported questionnaires. Lesion and brain volumes were analyzed and processed by the automated MSmetrix® software (Icometrix®, Leuven, Belgium). Spearman's correlation coefficient was used to evaluate the association of collected variables. A longitudinal logistic regression analysis was performed to find baseline correlates of CI at 12 months (T1). RESULTS: A total of 33 patients (56%) were defined as cognitively impaired at baseline, and 20 (38%) were defined as impaired at follow-up after 12 months. The mean raw scores and Z-scores of all the cognitive tests were significantly improved at T1 (p < 0.05). There was a statistically significant improvement in most PROM scores at T1 (p < 0.05) in comparison with baseline scores. Among the variables assessed, lower education and physical disability level at baseline correlated with impaired SDMT (OR: 1.68, p = 0.01; OR: 3.10, p = 0.02, respectively) and impaired BVMT-R (OR: 4.08, p=<0.001; OR: 4.82, p = 0.001, respectively) at T1. Neither baseline PROMs nor MRI volumetric parameters were predictive of cognitive performances at T1. CONCLUSIONS: These findings provide additional evidence that evolution of CI in MS may be a dynamic phenomenon and will not usually follow an inevitable, declining trajectory, and do not support the utility of PROMs in predicting CI in RRMS. The present study is still ongoing to determine whether our findings are confirmed at 2 and 3 years of follow-up.

Traumatic ulcerative granuloma with stromal eosinophilia (TUGSE): Case report of a 63-year-old male patient with a rare self-healing oral mucosal lesion.

Traumatic Ulcerative Granuloma with Stromal Eosinophilia (TUGSE)/Riga Fede disease is a rare mucosal and submucosal benign reactive inflammatory process, usually involving the tongue. Trauma is believed to be a major factor amongst the multiple pathogenic mechanisms that have been hypothesized in TUGSE. The lesion presents as an isolated indurated or even ulcerated mass, which may mimic, clinically a squamous cell carcinoma (SCC). We herein report a case of TUGSE in a 63-year-old male referred by his treating physician for high suspicion of tongue malignancy. Histopathological examination confirmed the diagnosis of TUGSE, without any evidence of a neoplasic, infectious or hematologic process. TUGSE occurs in patients with an age range of 41-60 years. Sufficiently deep biopsies with comprehensive immunohistochemical and molecular analyses are mandatory to confirm the benign nature of the lesion and to, definitely, rule out malignancy. This report highlights the need for adequate histological differential diagnosis to avoid inappropriate heavy treatments in a benign condition.

Clinical added value of interictal automated electrical source imaging in the presurgical evaluation of MRI-negative epilepsy: A real-life experience in 29 consecutive patients.

OBJECTIVE: During the presurgical evaluation, manual electrical source imaging (ESI) provides clinically useful information in one-third of the patients but it is time-consuming and requires specific expertise. This prospective study aims to assess the clinical added value of a fully automated ESI analysis in a cohort of patients with MRI-negative epilepsy and describe its diagnostic performance, by evaluating sublobar concordance with stereo-electroencephalography (SEEG) results and surgical resection and outcome. METHODS: All consecutive patients referred to the Center for Refractory Epilepsy (CRE) of St-Luc University Hospital (Brussels, Belgium) for presurgical evaluation between 15/01/2019 and 31/12/2020 meeting the inclusion criteria, were recruited to the study. Interictal ESI was realized on low-density long-term EEG monitoring (LD-ESI) and, whenever available, high-density EEG (HD-ESI), using a fully automated analysis (Epilog PreOp, Epilog NV, Ghent, Belgium). The multidisciplinary team (MDT) was asked to formulate hypotheses about the epileptogenic zone (EZ) location at sublobar level and make a decision on further management for each patient at two distinct moments: i) blinded to ESI and ii) after the presentation and clinical interpretation of ESI. Results leading to a change in clinical management were considered contributive. Patients were followed up to assess whether these changes lead to concordant results on stereo-EEG (SEEG) or successful epilepsy surgery. RESULTS: Data from all included 29 patients were analyzed. ESI led to a change in the management plan in 12/29 patients (41%). In 9/12 (75%), modifications were related to a change in the plan of the invasive recording. In 8/9 patients, invasive recording was performed. In 6/8 (75%), the intracranial EEG recording confirmed the localization of the ESI at a sublobar level. So far, 5/12 patients, for whom the management plan was changed after ESI, were operated on and have at least one-year postoperative follow-up. In all cases, the EZ identified by ESI was included in the resection zone. Among these patients, 4/5 (80%) are seizure-free (ILAE 1) and one patient experienced a seizure reduction of more than 50% (ILAE 4). CONCLUSIONS: In this single-center prospective study, we demonstrated the added value of automated ESI in the presurgical evaluation of MRI-negative cases, especially in helping to plan the implantation of depth electrodes for SEEG, provided that ESI results are integrated into the whole multimodal evaluation and clinically interpreted.

Patient-reported outcome measurements in a selective cohort of relapsing-remitting multiple sclerosis patients: relationships with physical disability, cognitive impairment, and MRI-derived metrics.

BACKGROUND: The added value of patient-reported outcome measures (PROMs) in addition to standard clinical outcome tools in the assessment of relapsing-remitting multiple sclerosis (RRMS) patients' status is increasingly recognized. PROMs facilitate the detection of hidden aspects of MS and help to integrate the patient's subjective experience of health-related quality of life (HRQoL) status and treatment satisfaction in a holistic way. However, the relationship between PROMs and clinical and cognitive status has been scarcely investigated up to now. OBJECTIVE: To investigate the association of PROMs with physical and cognitive disability in a cohort of RRMS patients at initiation of a new disease-modifying treatment. METHODS: In this cross-sectional bicenter study, 59 consecutive RRMS patients underwent neurological examination with EDSS assessment, comprehensive cognitive tests (BVMT-R, SDMT, CVLT-II) and a set of self-reported questionnaires. Lesion and brain volumes were analyzed and processed by the automated MSmetrix® software (Icometrix®, Leuven, Belgium). Spearman's correlation coefficient was used to evaluate the association of collected variables. A cross-sectional logistic regression analysis was performed to find baseline correlates of cognitive impairment. RESULTS: Of the 59 RRMS patients (mean age 39 ± 9.8 years, 79.7% female, median EDSS 2.0), 33 (56%) had cognitive impairment. While almost all dimensions of health, explored by PROMs, were impacted in the overall sample, no significant difference was observed in patients with and without cognitive impairment. All PROMs were significantly associated with EDSS (R = 0.37-0.55; p < 0.05), except for the psychological component of MSIS-29, BDI and DEX-Q scores. No significant correlation was found between PROMs and cognitive performances. The cross-sectional logistic regression analysis included age, gender (female), education, EDSS, hippocampus and FLAIR lesion volumes as significant predictors of cognitive impairment. CONCLUSIONS: The data highlight that PROMs provide valuable information on the well-being of PwMS closely paralleling the extent of MS-related disability, as measured by the EDSS. Additional research should determine the relevance of PROMs as longitudinal outcome measures.

Long-term survival in patients with IDH-wildtype glioblastoma: clinical and molecular characteristics.

BACKG ROUND: Glioblastoma is an aggressive tumor that has a dismal prognosis even with multimodal treatment. However, some patients survive longer than expected. The objective of this study was to revisit patients diagnosed with glioblastoma according to the 2021 WHO classification and analyze clinical and molecular characteristics associated with long-term survival (LTS). METHODS: We retrospectively analyzed 120 IDH-wildtype glioblastomas operated on at our institution between 2013 and 2018. We divided them into LTS patients, surviving more than 3 years, and non-LTS patients, and then compared their features. Additionally, we performed DNA methylation-based brain tumor classification in LTS patients. RESULTS: Sixteen patients were long-term survivors. Age < 70 years, MGMT promoter methylation, extent of resection ≥ 95%, and administration of radiochemotherapy were associated with LTS (P = 0.005, P < 0.001, P = 0.048, and P = 0.008, respectively). In addition, when these factors were combined, the probability of LTS was 74% (95% CI: 62--84). The methylome analysis confirmed the diagnosis of glioblastoma in the majority of the tested LTS patients. Regarding subtypes, 29% of cases were mesenchymal (MES), 43% were RTK1, and 29% were RTK2. Interestingly, RTK1 and RTK2 cases tended to have longer overall survival than MES cases (P = 0.057). Moreover, the only tested LTS patient with an unmethylated MGMT promoter had an "adult-type diffuse high-grade glioma, IDH-wildtype, subtype E" rather than a glioblastoma. This tumor was characterized by multinucleated giant cells and a somatic mutation in POLE. CONCLUSIONS: We suggest that glioblastoma patients with a combination of favorable prognostic factors can achieve LTS in 74% of cases. In addition, methylome analysis is important to ascertain the type of glioma in LTS patients, especially when the MGMT promoter is unmethylated.

Severe Neurological Involvement in an Adult with Shiga Toxin-Producing Escherichia coli-Hemolytic Uremic Syndrome Treated with Eculizumab.

A 68-year-old man with a medical history of hypertension was admitted to the emergency department for diffuse abdominal pain preceded by bloody diarrhea. Upon admission, neurological examination was normal, but he suddenly developed a left-sided hemiparesis. After a normal brain computed tomography, intravenous thrombolysis was administered for a suspicion of ischemic stroke. In the first laboratory investigations, hemoglobin was 16.9 g/dL, platelets 121 × 109/L (150-450), and serum creatinine 1.17 mg/dL. By the second hospital day, the platelet level dropped to 79 × 109/L, with haptoglobin at 0.12 g/L, 3% schistocytes, and normal ADAMTS13 activity (57%). Serum creatinine increased to 1.84 mg/dL with oliguria. The suspicion of thrombotic microangiopathy was supported by the identification of Shiga toxin genes stx1 and stx2 on a rectal swab and the isolation of an eaeA-negative Shiga toxin-producing E. coli O113:H4. The patient presented a generalized tonic-clonic seizure, and orotracheal intubation was required for decreased consciousness. Plasma exchange therapy was started, and eculizumab was given 6 days after symptoms onset. Brain magnetic resonance imaging (MRI) on day 13 showed symmetric hyperintensities within basal ganglia that disappeared on a second MRI on day 37. At 2-month follow-up, the patient had made a complete neurological and renal recovery and eculizumab therapy was stopped.

Erratum: Subacute brainstem ischemic syndrome in juvenile neurofibromatosis type 2: An under-recognized condition.

[This corrects the article DOI: 10.1002/ccr3.6686.].

Subacute brainstem ischemic syndrome in juvenile neurofibromatosis type 2: An underrecognized condition.

We report the case of a teenager with a neurofibromatosis Type 2 (NF2) presenting a locked-in syndrome due to a brainstem ischemic syndrome. The presence of sudden or rapidly worsening onset of neurological deficits in NF2 patients, should evoke this underknown entity and not only tumors as predisposed by NF2.

Relapsing-remitting Optic Neuropathy in an HIV-infected Patient: Secondary Auto-immune Optic Neuropathy or Infectious Optic Neuropathy? A Case Report and Review of the Literature.

It can be challenging to disentangle human immunodeficiency virus (HIV)-related infectious optic neuropathy and secondary triggered auto-immune disease when an HIV positive patient presents with vision loss. We report a 44-year-old untreated HIV positive Congolese woman who presented with two episodes of vision loss associated with pain in first her left eye and then her right eye and was diagnosed with a relapsing optic neuropathy. A correlation was observed between the clinical activity and cerebrospinal fluid viral load, CD4-count in the blood and magnetic resonance imaging signs of blood - optic nerve barrier breakdown. CD4 cell counts and viral loads are great clinical features to identify the type of acute optic neuropathy since differential diagnosis between an infectious optic neuropathy or an auto-immune induced optic neuropathy such as neuromyelitis optica spectrum disorder or immune reconstitution inflammatory syndrome can be puzzling.

MRI-guided DBS of STN under general anesthesia for Parkinson's disease: results and microlesion effect analysis.

BACKGROUND: The efficacy of the subthalamic nucleus (STN) stimulation for Parkinson's disease has been widely established. The microlesion effect (MLE) due to deep brain stimulation (DBS) electrode implantation has been reputed to be a good predictor for long-term efficacy of the procedure but its analysis in asleep implantation is still unclear. We thus analyzed MLE rate in our strategy of targeting the STN on MRI under general anesthesia and its correlation with our long-term results. METHOD: We retrospectively analyzed 32 consecutive parkinsonian patients implanted with a DBS targeting the STN bilaterally under general anesthesia between October 2013 and December 2020. Targeting was performed after head frame and localizer placement using a stereotactic peroperative robotic 3D fluoroscopy (Artis Zeego, Siemens) fused with preoperative CT and MRI data. We collected intraoperative data, postoperative occurrence of MLE, modification of Unified Parkinson Disease Rating Scale item III (UPDRS III) postoperatively and at subsequent visit, as well as reduction of medication. RESULTS: The mean operative time was 223 min. No permanent complication occurred. MLE was observed in 90.7%. The mean follow-up time was 17 months. The UPDRS III for the off medication/on stimulation condition improved by 64.8% from baseline. The mean dose reduction of Prolopa after the surgical procedure was 31.3%. CONCLUSIONS: Direct targeting of STN under general anesthesia based on preoperative CT and MRI data fused with a preoperative 3D fluoroscopy is safe. It allows for a high rate of postoperative MLE (90.7%) and results in prolonged clinical improvement.

GNA11-mutated Sturge-Weber syndrome has distinct neurological and dermatological features.

BACKGROUND AND PURPOSE: Sturge-Weber syndrome (SWS) is a neurocutaneous disorder characterized by clinical manifestations involving the brain, eye and skin. SWS is commonly caused by somatic mutations in G protein subunit Alpha Q (GNAQ). Five cases of subunit Alpha 11 (GNA11) mutations have been reported. We studied phenotypic features of GNA11-SWS and compared them with those of classic SWS. METHODS: Within two European multidisciplinary centers we looked for patients with clinical characteristics of SWS and a GNA11 mutation. Clinical and radiological data were collected retrospectively and prospectively. RESULTS: We identified three patients with SWS associated with a somatic GNA11 mutation. All had disseminated capillary malformation (CM) and hyper- or hypotrophy of an extremity. At birth, the CMs of the face, trunk and limbs were pink and patchy, and slowly darkened with age, evolving to a purple color. Two of the patients had glaucoma. All had neurological symptoms and moderate brain atrophy with a lower degree of severity than that classically associated with SWS. Susceptibility-weighted imaging (SWI) and contrast-enhanced fluid-attenuated inversion recovery (FLAIR) magnetic resonance imaging demonstrated the best sensitivity to reveal the pial angiomas. CONCLUSIONS: We have differentiated two distinct clinical/radiological phenotypes of SWS; GNAQ- and GNA11-SWS. The classic GNAQ-SWS is characterized by a homogeneous dark-red CM, commonly associated with underlying soft tissue hypertrophy. The CM in GNA11-SWS is more reticulate and darkens with time, and the neurological picture is milder. SWI and post-contrast FLAIR sequences appear to be necessary to demonstrate leptomeningeal angiomatosis. Anti-epileptic medication or future targeted therapies may be useful, as in classic SWS.

Optic Neuropathy Revealing Severe Superficial Siderosis in the Setting of Long-standing Low-grade Intracranial Neoplasm.

Two cases of optic neuropathy due to superficial siderosis (SS) are reported in two patients, aged 29 and 38 years, operated for intracranial neoplasms, the first one with a desmoplasic infantile ganglioglioma excised in 1991, and the other one with a pilocytic astrocytoma, operated on in 1997, 1998 and 2016. Both patients presented with progressive loss of visual acuity, as a result of bilateral optic nerve atrophy, as well as unsteadiness, ataxic gait and hearing loss. Magnetic resonance imaging (MRI) of the brain and spine, including gradient echo (GRE) T2-weighted acquisitions, revealed thin optic nerves and strong hypointensity with susceptibility artefacts corresponding to haemosiderin deposits within the meningeal layers of the spine, the infra- and supratentorial spaces of the brain and the peri-optic sheaths in both patients. The cerebrospinal fluid (CSF) was macroscopically haemorrhagic in one patient, who underwent a dynamic myelography, which failed to reveal any trans-dural CSF leakage. Neuro-ophthalmological symptoms due to SS, such as visual acuity loss, have been scarcely reported. MRI using GRE T2-weighted sequences highlighting the presence of haemosiderin deposits plays a key role in the diagnosis of this condition. Treatment should aim at preventing haemosiderin deposition by treating the cause of the subarachnoid bleeding.

Sino-Orbital Aspergillosis in a Kidney Transplant Recipient.

Sino-orbital aspergillosis is a rare and severe infection mostly seen in immunocompromised individuals in which diagnosis may be challenging with potentially life-threatening consequences. Infection usually starts in the paranasal sinuses with secondary spreading to the adjacent orbits. Here, we report the case of a kidney transplant recipient who presented with proven invasive sino-orbital aspergillosis resulting in irreversible loss of vision despite surgical management and antifungal therapy. We review the literature with a focus on clinical presentation, diagnostic tools, and recommended treatment in the context of kidney transplantation.

Rapidly Reversible Leukoencephalopathy After Acute Kidney Graft Rejection in a Patient With Systemic Lupus Erythematosus.

The finding of white matter damage on brain magnetic resonance imaging may correspond to a wide variety of etiologies. The differential diagnosis may be particularly difficultin immunocompromised patients with a specific autoimmune disease or who are receiving medications after a solid-organ transplant. Herein, we describe the case of a 22-year-old woman who developed serious neurological complications after an acute rejection of a kidney graft that she had received a few months previous to treat a systemic lupus erythematosus-related nephritis.We discuss the possible hypotheses underlying the development of acute leukoencephalopathy in this setting.

Case report: Motor neuron disease phenotype associated with symptomatic copper deficiency: Challenging diagnosis and treatment.

Copper deficiency is an acquired condition that can lead to neurologic dysfunctions, such as myelopathy, motor neuron impairment, polyneuropathy, cognitive impairment, and optic nerve neuropathy. Associated biological findings are low serum copper and ceruloplasmin levels with low copper urinary excretion. We report the case of a previously healthy 59-year-old man who presented a complex neurological picture starting with symptoms and radiological signs consistent with degenerative myelopathy in the presence of persisting low serum copper and ceruloplasmin despite oral and intravenous copper supplementation. Over time, his symptoms evolved into a motor neuron disease evocating an amyotrophic lateral sclerosis (ALS) phenotype. The potential role of copper deficiency is discussed, together with the difficulties in biomonitoring copper supplementation.