Search

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.

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.

Summary: 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).

Abstract We report the case of a teenager with 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.

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.

Abstract 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.

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.

Abstract Primary cutaneous apocrine adenocarcinoma (PCAC) is an extremely rare neoplasm involving the sweat glands. Due to a lack of cases, there is no consensus for the systemic treatment of locally advanced or metastatic PCAC. Anti‐androgen therapy may have activity in inoperable or metastatic PCAC with high androgen receptor (AR) expression.

Abstract Progressive multifocal leukoencephalopathy (PML) may develop in follicular lymphoma patients treated with bendamustine‐rituximab. In this report, treatment with pembrolizumab successfully inhibited the clinical progression of PML by promoting radiologically demonstrated immune restoration inflammatory syndrome (IRIS), allowing complete clearance of the virus. These findings may further support the use of pembrolizumab in PML with special consideration for the potential occurrence of IRIS.

Susac syndrome (SS) is a central nervous system vasculitis characterized by the clinical triad of encephalopathy, sensorineural hearing loss, and visual disturbance caused by branch retinal artery occlusion. It is considered as an inflammatory disorder, and an autoimmune etiology is suggested. A 29-year-old man with a history of recent cocaine abuse developed the clinical features of SS. Toxicological analysis including hair testing revealed that cocaine had been adulterated with levamisole. After an initial clinical improvement following corticosteroid therapy, the introduction of mycophenolate mofetil was justified a few weeks later by the progression (or relapse) of the retinal injury, followed by complete recovery. The presence of levamisole has been documented in patients with multifocal inflammatory leukoencephalopathy (MIL). Further investigations are needed to determine if levamisole as an adulterant of cocaine could also play a role in the development of rapidly progressive leukoencephalopathy in young men, with Susac or Susac-like syndromes as possible variants of MIL.

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.

Teaching Point: Central nervous system adverse effects of cytarabine treatment include aseptic meningitis, myelopathy, and more rarely, encephalopathy, seizures, and cerebellar dysfunction. This case illustrates a cytarabine-induced encephalitis with predominant cerebellar involvement.

Teaching Point: Contrast-enhanced FLAIR images have unsurpassed value for the radiological depiction of hypertensive papilledema. FLAIR acquisition should therefore be performed after intravenous contrast, especially in the of work-up of intracranial hypertension and/or tumor.

Abstract Background Amyloid infiltration of endocrine glands has been reported, mostly in the thyroid, pancreas, adrenals, and testes, but affected patients do not frequently exhibit overt endocrine insufficiency. Here we report the case of a patient with complete anterior hypopituitarism probably due to a known systemic amyloidosis. Case presentation Our male Caucasian patient was diagnosed with Crohn’s disease at the age of 22 years. At the age of 37, he developed secondary renal amyloidosis, which resulted in end-stage renal failure. He received a living-donor kidney transplant at the age of 57, without initial complication. Two months later, he developed extreme fatigue, weight loss, and dyspnea. A hormonal evaluation demonstrated complete anterior pituitary insufficiency. A pituitary magnetic resonance imaging was performed and showed a diffusely hypointense anterior gland on both T1-weighted and T2-weighted images with reduced gadolinium enhancement, highly suggestive of amyloid infiltration of the pituitary. Treatment was initiated with levothyroxine, orally administered hydrocortisone, and testosterone enanthate, rapidly allowing progressive marked clinical improvement and nearly complete resolution of symptoms. Conclusions Pituitary amyloid infiltration should be considered in patients with a known systemic amyloidosis who develop symptoms of hypopituitarism and magnetic resonance imaging features compatible with protein deposits.

A 26-year-old woman presented with severe postpartum headaches. Magnetic resonance imaging (MRI) revealed a symmetric, heterogeneous enlargement of the pituitary gland. Three months later, she developed central diabetes insipidus. A diagnosis of postpartum hypophysitis was suspected and corticosteroids were prescribed. Six months later, the pituitary mass showed further enlargement and characteristics of a necrotic abscess with a peripheral shell and infiltration of the hypothalamus. Transsphenoidal surgery was performed, disclosing a pus-filled cavity which was drained. No bacterial growth was observed, except a single positive blood culture for Staphylococcus aureus, considered at that time as a potential contaminant. A short antibiotic course was, however, administered together with hormonal substitution for panhypopituitarism. Four months after her discharge, severe headaches recurred. Pituitary MRI was suggestive of a persistent inflammatory mass of the sellar region. She underwent a new transsphenoidal resection of a residual abscess. At that time, the sellar aspiration fluid was positive for Staphylococcus aureus and she was treated with antibiotics for 6 weeks, after which she had complete resolution of her infection. The possibility of a pituitary abscess, although rare, should be kept in mind during evaluation for a necrotic inflammatory pituitary mass with severe headaches and hormonal deficiencies.

The aim of this study was to investigate the relationship between stroke lesion location and the resulting somatosensory deficit. We studied exteroceptive and proprioceptive somatosensory symptoms and stroke lesions in 38 patients with first-ever acute stroke. The Erasmus modified Nottingham Sensory Assessment was used to clinically evaluate somatosensory functioning in the arm and hand within the first week after stroke onset. Additionally, more objective measures such as the perceptual threshold of touch and somatosensory evoked potentials were recorded. Non-parametric voxel-based lesion-symptom mapping was performed to investigate lesion contribution to different somatosensory deficits in the upper limb. Additionally, structural connectivity of brain areas that demonstrated the strongest association with somatosensory symptoms was determined, using probabilistic fiber tracking based on diffusion tensor imaging data from a healthy age-matched sample. Voxels with a significant association to somatosensory deficits were clustered in two core brain regions: the central parietal white matter, also referred to as the sensory component of the superior thalamic radiation, and the parietal operculum close to the insular cortex, representing the secondary somatosensory cortex. Our objective recordings confirmed findings from clinical assessments. Probabilistic tracking connected the first region to thalamus, internal capsule, brain stem, postcentral gyrus, cerebellum, and frontal pathways, while the second region demonstrated structural connections to thalamus, insular and primary somatosensory cortex. This study reveals that stroke lesions in the sensory fibers of the superior thalamocortical radiation and the parietal operculum are significantly associated with multiple exteroceptive and proprioceptive deficits in the arm and hand.

A 75-year-old woman was admitted to ICU with coma following Streptococcus pneumoniae meningitis with bacteremia. Her Glasgow Coma Scale (GCS) score fluctuated around 4 to 6 over the next four weeks. There was no evidence of increased intracranial pressure (ICP). Electroencephalogram (EEG) showed only diffuse aspecific slowing. Impaired cerebral blood flow (CBF) autoregulation was suggested at transcranial Doppler (TCD). Repeated brain magnetic resonance imaging (MRI) examination failed to demonstrate venous thrombosis, arterial ischemic stroke, or brain abscesses but revealed diffuse but reversible cortical cytotoxic edema at diffusion-weighted (DW) sequences. The brain FDG-positron emission tomography (FDG-PET) showed diffuse cortical hypometabolism. The patient unexpectedly experienced a complete neuropsychological recovery the next few weeks. The suggested hypothesis to explain this unusual disease course could be a transient alteration of CBF autoregulation due to some degree of diffuse subcortical microangiopathy. A concomitant reduction of brain metabolism probably prevented the progression towards cortical irreversible ischemic damage.

BACKGROUND:Aberrant functional connectivity in brain networks associated with motor impairment after stroke is well described, but little is known about the association with somatosensory impairments. AIM:The objective of this cross-sectional observational study was to investigate the relationship between brain functional connectivity and severity of somatosensory impairments in the upper limb in the acute phase post stroke. METHODS:Nineteen first-ever stroke patients underwent resting-state functional magnetic resonance imaging (rs-fMRI) and a standardized clinical somatosensory profile assessment (exteroception and higher cortical somatosensation) in the first week post stroke. Integrity of inter- and intrahemispheric (ipsilesional and contralesional) functional connectivity of the somatosensory network was assessed between patients with severe (Em-NSA< 13/32) and mild to moderate (Em-NSA> 13/32) somatosensory impairments. RESULTS:Patients with severe somatosensory impairments displayed significantly lower functional connectivity indices in terms of interhemispheric (p = 0.001) and ipsilesional intrahemispheric (p = 0.035) connectivity compared to mildly to moderately impaired patients. Significant associations were found between the perceptual threshold of touch assessment and interhemispheric (r = -0.63) and ipsilesional (r = -0.51) network indices. Additional significant associations were found between the index of interhemispheric connectivity and light touch (r = 0.55) and stereognosis (r = 0.64) evaluation. CONCLUSION:Patients with more severe somatosensory impairments have lower inter- and ipsilesional intrahemispheric connectivity of the somatosensory network. Lower connectivity indices are related to more impaired exteroception and higher cortical somatosensation. This study highlights the importance of network integrity in terms of inter- and ipsilesional intrahemispheric connectivity for somatosensory function. Further research is needed investigating the effect of therapy on the re-establishment of these networks.

Among other autonomic dysfunctions complicating acute spinal cord injury, deep hypothermia is rare but may induce serious cardiovascular complications. There are few pharmacological options to influence hypothermia. A 66-year-old woman was transferred to the intensive care unit (ICU) for serious cardiac arrhythmias (atrial fibrillation and asystole) in the context of a deep hypothermia (axillary temperature below 32°C). She had been admitted to the hospital two months before for an acute L4-L5 infectious spondylodiscitis without any initial neurological deficit. After surgery for epidural abscess drainage, she became paraplegic due to spinal cord infarction (from C7 to T6 levels) in the upper territory of the anterior spinal artery. In the ICU, the patient experienced several episodes of asystole and hypotension associated with a core body temperature below 35°C. Common causes of hypothermia (drugs, hypothyroidism, etc.) were excluded. A definitive pacemaker had to be inserted, but hypotension persisted. The prescription of oral progesterone (200 mg·d−1) helped to maintain a core temperature higher than 35°C, with a withdrawal of vasopressors. This case report illustrates that patients with incomplete spinal cord injury may present with delayed and deep hypothermia leading to serious cardiovascular complications. Progesterone could be able to influence positively central and peripheral thermal regulation.

We report on two cases of transient akinetic mutism after massive subarachnoid haemorrhage due to the rupture of an intracranial aneurysm of the anterior cerebral artery (ACA). In the two cases, vasospasm could not be demonstrated by imaging studies throughout the clinical course. Both patients shared common radiological features: a hydrocephalus due to haemorrhagic contamination of the ventricular system and a mass effect of a subpial hematoma on the borders of the corpus callosum. Patients were also investigated using auditory event-related evoked potentials at acute stage. In contrast to previous observations of akinetic mutism, P300 wave could not be recorded. Both patients had good recovery and we hypothesized that this unexpectedly favourable outcome was due to the absence of permanent structural damage to the ACA territory, with only transient dysfunction due to a reversible mass effect on cingulate gyri.

The clinical applicability of brain oxygenation mapping using the MOBILE (Mapping of Oxygen By Imaging Lipids relaxation Enhancement) magnetic resonance (MR) technique was assessed in the clinical setting of normal brain and of acute cerebral ischemia as a founding proof-of-concept translational study. Changes in the oxygenation level within healthy brain tissue can be detected by analyzing the spin-lattice proton relaxation ('Global T1' combining water and lipid protons) because of the paramagnetic properties of molecular oxygen. It was hypothesized that selective measurement of the relaxation of the lipid protons ('Lipids T1') would result in enhanced sensitivity of pO2 mapping because of higher solubility of oxygen in lipids than in water, and this was demonstrated in pre-clinical models using the MOBILE technique. In the present study, 12 healthy volunteers and eight patients with acute (48-72 hours) brain infarction were examined with the same clinical 3T MR system. Both Lipids R1 (R1 = 1/T1) and Global R1 were significantly different in the infarcted area and the contralateral unaffected brain tissue, with a higher statistical significance for Lipids R1 (median difference: 0.408 s-1; p

Brain blood barrier breakdown as assessed by contrast-enhanced (CE) T1-weighted MR imaging is currently the standard radiological marker of inflammatory activity in multiple sclerosis (MS) patients. Our objective was to evaluate the performance of an alternative model assessing the inflammatory activity of MS lesions by texture analysis of T2-weighted MR images. Twenty-one patients with definite MS were examined on the same 3.0T MR system by T2-weighted, FLAIR, diffusion-weighted and CE-T1 sequences. Lesions and mirrored contralateral areas within the normal appearing white matter (NAWM) were characterized by texture parameters computed from the gray level co-occurrence and run length matrices, and by the apparent diffusion coefficient (ADC). Statistical differences between MS lesions and NAWM were analyzed. ROC analysis and leave-one-out cross-validation were performed to evaluate the performance of individual parameters, and multi-parametric models using linear discriminant analysis (LDA), partial least squares (PLS) and logistic regression (LR) in the identification of CE lesions. ADC and all but one texture parameter were significantly different within white matter lesions compared to within NAWM (p < 0.0167). Using LDA, an 8-texture parameter model identified CE lesions with a sensitivity Se = 70% and a specificity Sp = 76%. Using LR, a 10-texture parameter model performed better with Se = 86% / Sp = 84%. Using PLS, a 6-texture parameter model achieved the highest accuracy with Se = 88% / Sp = 81%. Texture parameter from T2-weighted images can assess brain inflammatory activity with sufficient accuracy to be considered as a potential alternative to enhancement on CE T1-weighted images.