Gene- and Gender-Related Decrease in Serum BDNF Levels in Alzheimer's Disease.

Brain-derived neurotrophic factor (BDNF) has a protective role in Alzheimer's disease (AD). Oxidative stress and inflammatory cytokines are potentially implicated in AD risk. In this study, BDNF was detected in serum of AD and mild cognitive impairment (MCI) patients and investigated in association with gene polymorphisms of BDNF (Val66Met and C270T), of some oxidative stress-related genes (FOXO3A, SIRT3, GLO1, and SOD2), and of interleukin-1 family genes (IL-1α, IL-1ß, and IL-38). The APOE status and mini-mental state examination (MMSE) score were also evaluated. Serum BDNF was significantly lower in AD (p = 0.029), especially when comparing the female subsets (p = 0.005). Patients with BDNFVal/Val homozygous also had significantly lower circulating BDNF compared with controls (p = 0.010). Moreover, lower BDNF was associated with the presence of the T mutant allele of IL-1α(rs1800587) in AD (p = 0.040). These results were even more significant in the female subsets (BDNFVal/Val, p = 0.001; IL-1α, p = 0.013; males: ns). In conclusion, reduced serum levels of BDNF were found in AD; polymorphisms of the IL-1α and BDNF genes appear to be involved in changes in serum BDNF, particularly in female patients, while no effects of other gene variants affecting oxidative stress have been found. These findings add another step in identifying gender-related susceptibility to AD.

An experience-based review of HIFU in functional interventional neuroradiology: transcranial MRgFUS thalamotomy for treatment of tremor.

Tremor is a common and very disabling symptom in patients with essential tremor and Parkinson's disease. In the recent years, transcranial ablation of thalamic nuclei using magnetic resonance guided high-intensity focused ultrasound has emerged as a minimally invasive treatment for tremor. The aim of this review is to discuss, in the light of our single-center experience, the technique, current applications, results, and future perspectives of this novel technology.

Staged magnetic resonance-guided focused ultrasound thalamotomy for the treatment of bilateral essential tremor and Parkinson's disease related tremor: a systematic review and critical appraisal of current knowledge.

Introduction: Essential tremor (ET) and Parkinson's Disease (PD) are debilitating neurodegenerative disorders characterized by tremor as a predominant symptom, significantly impacting patients' quality of life. Magnetic Resonance-guided Focused Ultrasound (MRgFUS) Thalamotomy is an innovative therapeutic option for the treatment of unilateral medically refractory tremor with fewer adverse effects compared to traditional surgical interventions. A recent CE approval allows appropriate patients to have their second side treated. Objective: The objective of this systematic review was to analyze available current knowledge about the use of MRgFUS for the treatment of bilateral ET and PD related tremor, to identify the effectiveness and the risks associated with bilateral treatment. Methods: Eligible studies were identified by searching published studies in PubMed and Scopus databases from May 2014 to January 2024 and by identifying ongoing studies registered on the clinicaltrials.gov website. Data were summarized by considering the following information topics: the number of patients involved, the selected lesion target, the assessment tool used to evaluate clinical changes, the observed improvement, the reported side effects, and the time interval between the two treatments. The study was registered in PROSPERO (ID: CRD42024513178). Results: Nine studies were eligible for this review, 7 for ET and 2 for PD. The involved population included a variable number of patients, ranging from 1 to 11 subjects for ET and from 10 to 15 subjects for PD. The main lesional targets were the ventral intermediate nucleus of the thalamus, the pallidothalamic tract and the cerebellothalamic tract bilaterally. All studies investigated the tremor relief through the Clinical Rating Scale for Tremor (CRST) in patients with ET, and through the Unified Parkinson's Disease Rating Scale (UPDRS) in patients with PD. A variable degree of improvement was observed, with all patients expressing overall satisfaction with the bilateral treatment. Adverse events were mild and transient, primarily involving gait disturbances, dysarthria, and ataxia. A standardized protocol for administering the two consecutive treatments was not identifiable; typically, the timing of the second treatment was delayed by at least 6 months. Conclusion: Available evidence supports the effectiveness and safety of staged bilateral MRgFUS treatments for ET and PD-related tremor.

Early re-emerging tremor after MRgFUS thalamotomy: case-control analysis of procedural and imaging features.

Purpose: This study aimed to identify possible prognostic factors determining early tremor relapse after Magnetic Resonance guided Focused Ultrasound Surgery (MRgFUS) thalamotomy in patients with essential tremor (ET) and Parkinson's disease (PD). Methods: Nine patients (six ET and three PD) who underwent Vim MRgFUS thalamotomy in a single institution and developed early re-emergent tremor were analyzed. A control group of patients matched pairwise for sex, pathology, age, disease duration, and skull density ratio (SDR) was selected to compare the technical-procedural data and MR imaging evidence. MR imaging findings compared between groups included lesion shape and volume in multiparametric sequences, as well as Fractiona Anisotropy (FA) and Apparent Diffusion Coefficient (ADC) values derived from Diffusion Tensor Imaging Diffusion Weighted Imaging (DTI) and Diffusion Weighted Imaging (DWI) sequences. Results: We did not find statistically significant differences in gender and age between the two groups. Technical and procedural parameters were also similar in both treatment groups. In MRI analysis, we found lesions of similar size but with greater caudal extension in the control group with stable outcomes compared to patients with tremor relapse. Conclusion: In our analysis of early recurrences after thalamotomy with focused ultrasound, there were neither technical and procedural differences nor prognostic factors related to lesion size or ablation temperatures. Greater caudal extension of the lesion in patients without recurrence might suggest the importance of spatial consolidation during treatment.

Facial emotion recognition and judgment of affective scenes in Parkinson's disease.

Emotional dysfunctions in Parkinson's disease (PD) remain a controversial issue. While previous investigations showed compromised recognition of expressive faces in PD, no studies evaluated potential deficits in recognizing the emotional valence of affective scenes. This study aimed to investigate both facial emotion recognition performance and the ability to judge affective scenes in PD patients. Forty PD patients (mean age ± SD: 64.50 ± 8.19 years; 27 men) and forty healthy subjects (64.95 ± 8.25 years; 27 men) were included. Exclusion criteria were previous psychiatric disorders, previous Deep Brain Stimulation, and cognitive impairment. Participants were evaluated through the Ekman 60-Faces test and the International Affective Picture System. The accuracy in recognizing the emotional valence of facial expressions and affective scenes was compared between groups using linear mixed models. Pearson's correlation was performed to test the association between accuracy measures. The groups did not differ in sex, age, education, and Mini-Mental State Examination scores. Patients showed a lower recognition accuracy of facial expressions (68.54 % ± 15.83 %) than healthy participants (78.67 % ± 12.04 %; p < 0.001). Specifically, the PD group was characterized by lower recognition of faces expressing fear, sadness, and anger than the control group (all p < 0.020). No difference was detected for faces expressing disgust, surprise, and happiness (all p ≥ 0.25). Furthermore, patients showed lower accuracy in recognizing the emotional valence of affective scenes (66.75 % ± 14.59 %) than healthy subjects (74.83 % ± 12.65 %; p = 0.010). Pearson's correlations indicated that higher accuracy in recognizing the emotional facial expressions was associated with higher accuracy in classifying the valence of affective scenes in patients (r = 0.57, p < 0.001) and control participants (r = 0.57, p < 0.001). Our study suggested maladaptive affective processing in PD, leading patients to misinterpret both facial expressions and the emotional valence of complex evocative scenes.

Cognitive safety of focused ultrasound thalamotomy for tremor: 1-year follow-up results of the COGNIFUS part 2 study.

Introduction: In the COGNitive in Focused UltraSound (COGNIFUS) study, we examined the 6-month cognitive outcomes of patients undergoing MRgFUS thalamotomy. This study endorsed the safety profile of the procedure in terms of cognitive functions that cannot be evaluated in real-time during the procedure unlike other aspects. The aim of the COGNIFUS Part 2 study was to investigate the cognitive trajectory of MRgFUS patients over a 1-year period, in order to confirm long-term safety and satisfaction. Methods: We prospectively evaluated the cognitive and neurobehavioral profile of patients with essential tremor (ET) or Parkinson's Disease (PD) related tremor undergoing MRgFUS thalamotomy at 1 year-follow-up following the treatment. Results: The sample consists of 50 patients (male 76%; mean age ± SD 69.0 ± 8.56; mean disease duration ± SD 12.13 ± 12.59; ET 28, PD 22 patients). A significant improvement was detected at the 1 year-follow-up assessment in anxiety and mood feelings (Hamilton Anxiety rating scale 5.66 ± 5.02 vs. 2.69 ± 3.76, p ≤ <0.001; Beck depression Inventory II score 3.74 ± 3.80 vs. 1.80 ± 2.78, p = 0.001), memory domains (Rey Auditory Verbal Learning Test, immediate recall 31.76 ± 7.60 vs. 35.38 ± 7.72, p = 0.001 and delayed recall scores 5.57 ± 2 0.75 vs. 6.41 ± 2.48), frontal functions (Frontal Assessment Battery score 14.24 ± 3.04 vs. 15.16 ± 2.74) and in quality of life (Quality of life in Essential Tremor Questionnaire 35.00 ± 12.08 vs. 9.03 ± 10.64, p ≤ 0.001 and PD Questionnaire -8 7.86 ± 3.10 vs. 3.09 ± 2.29, p ≤ 0.001). Conclusion: Our study supports the long-term efficacy and cognitive safety of MRgFUS treatment for ET and PD.

Increased glucosylsphingosine levels and Gaucher disease in GBA1-associated Parkinson's disease.

INTRODUCTION: Gaucher's disease (GD) is caused by biallelic mutations in the GBA1 gene, leading to reduced glucocerebrosidase (GCase) activity and substrate (glucosylceramide and glucosylsphingosine, GlcSph) accumulation. GBA1 variant carriers are at risk of Parkinson's disease (PD), but only those with biallelic mutations cross the threshold of GCase reduction, leading to substrate accumulation and GD. The link between GBA1 mutations, GD and PD is not fully understood. Here we aimed at reporting the results of a large PD population screening with dried blood spot tests for GD. METHODS: We measured GCase activity and GlcSph levels in 1344 PD patients with dried blood spot tests, and performed GBA1 genetic sequencing. RESULTS: While the GCase activity was reduced in GBA1-PD carriers compared to wild type PD, GlcSph was increased in GBA1-PD compared to GBA1-controls, regardless of the underlying type of GBA1 variant. 13.6 % and 0.4 % of PD patients had mono- or biallelic GBA1 mutations respectively. GCase deficiency, lipid accumulation and clinical manifestations of GD was detected in five PD patients with biallelic GBA1 mutations, of whom four had a risk combined with a GD causing variant. CONCLUSIONS: GlcSph appearing higher in PD may represent a reliable biomarker of the disease and deserves to be further investigated. This study highlights the importance of screening PD patients for possible underlying GD, which is a treatable condition that should not be missed. We diagnosed GD cases carrying a "risk" variant in one allele, which is an unprecedented finding deserving further investigation.

Cognitive outcomes after focused ultrasound thalamotomy for tremor: Results from the COGNIFUS (COGNitive in Focused UltraSound) study.

INTRODUCTION: Magnetic resonance-guided focused ultrasound (MRgFUS) thalamotomy is an innovative method for the unilateral treatment of essential tremor (ET) and Parkinson's disease (PD) related tremor. Our aim was to assess cognitive changes following MRgFUS thalamotomy to better investigate its safety profile. METHODS: We prospectively investigated the cognitive and neurobehavioral profile of patients consecutively undergoing MRgFUS within a 2-year period. Patients had a comprehensive clinical and neuropsychological assessment before and six months after MRgFUS thalamotomy. RESULTS: The final sample consisted of 40 patients (males 38; mean age±SD 67.7 ± 10.7; mean disease duration±SD 9.3 ± 5.6; ET 22, PD 18 patients). For the whole sample, improvements were detected in tremor (Fahn-Tolosa-Marin Clinical Rating Scale for tremor 35.79 ± 14.39 vs 23.03 ± 10.95; p < 0.001), anxiety feelings (Hamilton Anxiety rating scale 5.36 ± 3.80 vs 2.54 ± 3.28, p < 0.001), in the overall cognitive status (MMSE 25.93 ± 3.76 vs 27.54 ± 2.46, p 0.003; MOCA 22.80 ± 4.08 vs 24.48 ± 3.13, p < 0.001), and in quality of life (Quality of life in Essential Tremor Questionnaire 36.14 ± 12.91 vs 5.14 ± 6.90, p < 0.001 and PD Questionnaire-8 5.61 ± 4.65 vs 1.39 ± 2.33, p 0.001). No changes were detected in frontal and executive functions, verbal fluency and memory, abstract reasoning and problem-solving abilities. CONCLUSION: Our study moves a step forward in establishing the cognitive sequelae of MRgFUS thalamotomy and in endorsing effectiveness and safety.

Magnetic Resonance-guided Focused Ultrasound thalamotomy for refractory neuropathic pain: a systematic review and critical appraisal of current knowledge.

Background: Magnetic Resonance-guided Focused Ultrasound (MRgFUS) is an innovative therapeutical approach for medically refractory tremor. It is currently under investigation for other neurological diseases including refractory neuropathic pain (NP). Objective: The objective of this systematic review is to analyze available evidence about the effectiveness and safety profile of MRgFUS in the treatment of refractory NP. Methods: Eligible studies were identified by searching published studies in PubMed and Scopus databases from inception to December 2022 and by identifying ongoing studies registered on the clinicaltrials.gov website. The study was registered in PROSPERO (ID: CRD42021277154). Results: We found three published observational studies and nine ongoing studies. In published studies, the involved population ranged from 8 to 46 patients with overall 66 patients being included with NP or trigeminal neuralgia. The target lesion was in the posterior part of the central lateral nucleus of the thalamus, bilaterally. Outcomes were assessed at different times through the Visual Analog Scale, showing a variable degree of improvement. Adverse events were rare, mild, and transient (vertigo, paresthesias, and dysesthesias) with intracerebral bleeding being reported as major adverse event in one case only. Among ongoing studies, we found three prospective, randomized, sham-controlled, crossover trials (RCTs) and six observational studies. Inclusion criteria are previous failure of more than three pharmacological treatments and NP duration longer than 6 months. The thalamus is the main proposed target and measured outcomes are accuracy of the procedure and pain relief, with a follow-up period ranging from 1 week to 1 year. Conclusion: This systematic review suggests that, although high-quality studies are lacking, available evidence endorses the effectiveness and safety of MRgFUS in the management of NP. Ongoing RCTs will provide more robust data to understand benefits and risks of the procedure. Registration: PROSPERO (ID: CRD42021277154).

Effects of deep brain stimulation of the subthalamic nucleus on patients with Parkinson's disease: a machine-learning voice analysis.

Introduction: Deep brain stimulation of the subthalamic nucleus (STN-DBS) can exert relevant effects on the voice of patients with Parkinson's disease (PD). In this study, we used artificial intelligence to objectively analyze the voices of PD patients with STN-DBS. Materials and methods: In a cross-sectional study, we enrolled 108 controls and 101 patients with PD. The cohort of PD was divided into two groups: the first group included 50 patients with STN-DBS, and the second group included 51 patients receiving the best medical treatment. The voices were clinically evaluated using the Unified Parkinson's Disease Rating Scale part-III subitem for voice (UPDRS-III-v). We recorded and then analyzed voices using specific machine-learning algorithms. The likelihood ratio (LR) was also calculated as an objective measure for clinical-instrumental correlations. Results: Clinically, voice impairment was greater in STN-DBS patients than in those who received oral treatment. Using machine learning, we objectively and accurately distinguished between the voices of STN-DBS patients and those under oral treatments. We also found significant clinical-instrumental correlations since the greater the LRs, the higher the UPDRS-III-v scores. Discussion: STN-DBS deteriorates speech in patients with PD, as objectively demonstrated by machine-learning voice analysis.

Levodopa Equivalent Dose of Safinamide: A Multicenter, Longitudinal, Case-Control Study.

Background: Effects of dopaminergic medications used to treat Parkinson's disease (PD) may be compared with each other by using conversion factors, calculated as Levodopa equivalent dose (LED). However, current LED proposals on MAO-B inhibitors (iMAO-B) safinamide and rasagiline are still based on empirical approaches. Objectives: To estimate LED of safinamide 50 and 100 mg. Methods: In this multicenter, longitudinal, case-control study, we retrospectively reviewed clinical charts of 500 consecutive PD patients with motor complications and treated with (i) safinamide 100 mg (N = 130), safinamide 50 mg (N = 144), or rasagiline 1 mg (N = 97) for 9 ± 3 months and a control group of patients never treated with any iMAO-B (N = 129). Results: Major baseline features (age, sex, disease duration and stage, severity of motor signs and motor complications) were similar among the groups. Patients on rasagiline had lower UPDRS-II scores and Levodopa dose than control subjects. After a mean follow-up of 8.8-to-10.1 months, patients on Safinamide 50 mg and 100 mg had lower UPDRS-III and OFF-related UPDRS-IV scores than control subjects, who in turn had larger increase in total LED than the three iMAO-B groups. After adjusting for age, disease duration, duration of follow-up, baseline values and taking change in UPDRS-III scores into account (sensitivity analysis), safinamide 100 mg corresponded to 125 mg LED, whereas safinamide 50 mg and rasagiline 1 mg equally corresponded to 100 mg LED. Conclusions: We used a rigorous approach to calculate LED of safinamide 50 and 100 mg. Large prospective pragmatic trials are needed to replicate our findings.

Neurotrophins as Therapeutic Agents for Parkinson's Disease; New Chances From Focused Ultrasound?

Magnetic Resonance-guided Focused Ultrasound (MRgFUS) represents an effective micro-lesioning approach to target pharmaco-resistant tremor, mostly in patients afflicted by essential tremor (ET) and/or Parkinson's disease (PD). So far, experimental protocols are verifying the clinical extension to other facets of the movement disorder galaxy (i.e., internal pallidus for disabling dyskinesias). Aside from those neurosurgical options, one of the most intriguing opportunities of this technique relies on its capability to remedy the impermeability of blood-brain barrier (BBB). Temporary BBB opening through low-intensity focused ultrasound turned out to be safe and feasible in patients with PD, Alzheimer's disease, and amyotrophic lateral sclerosis. As a mere consequence of the procedures, some groups described even reversible but significant mild cognitive amelioration, up to hippocampal neurogenesis partially associated to the increased of endogenous brain-derived neurotrophic factor (BDNF). A further development elevates MRgFUS to the status of therapeutic tool for drug delivery of putative neurorestorative therapies. Since 2012, FUS-assisted intravenous administration of BDNF or neurturin allowed hippocampal or striatal delivery. Experimental studies emphasized synergistic modalities. In a rodent model for Huntington's disease, engineered liposomes can carry glial cell line-derived neurotrophic factor (GDNF) plasmid DNA (GDNFp) to form a GDNFp-liposome (GDNFp-LPs) complex through pulsed FUS exposures with microbubbles; in a subacute MPTP-PD model, the combination of intravenous administration of neurotrophic factors (either through protein or gene delivery) plus FUS did curb nigrostriatal degeneration. Here, we explore these arguments, focusing on the current, translational application of neurotrophins in neurodegenerative diseases.

Cerebello-Thalamo-Cortical MR Spectroscopy in Patients with Essential Tremor Undergoing MRgFUS Thalamotomy: A Pilot Study.

Previous literature studies explored the association between brain neurometabolic changes detected by MR spectroscopy and symptoms in patients with tremor, as well as the outcome after deep brain stimulation (DBS) treatment. The purpose of our study was to evaluate the possible changes in cerebello-thalamo-cortical neurometabolic findings using MR spectroscopy in patients submitted to MRgFUS thalamotomy. For this pilot study, we enrolled 10 ET patients eligible for MRgFUS thalamotomy. All patients were preoperatively submitted to 3T MR spectroscopy. Single-voxel MRS measurements were performed at the level of the thalamus contralateral to the treated side and the ipsilateral cerebellar dentate nucleus. Multivoxel acquisition was used for MRS at the level of the contralateral motor cortex. At the 6-month follow-up after treatment, we found a statistically significant increase in the Cho/Cr ratio at the level of the thalamus, a significant increase of the NAA/Cr ratio at the level of the dentate nucleus and a significant decrease of the NAA/Cho ratio at the level of the motor cortex. We found a significant positive correlation between cortical NAA/Cr and clinical improvement (i.e., tremor reduction) after treatment. A significant negative correlation was found between clinical improvement and thalamic and cerebellar NAA/Cr. Confirming some previous literature observations, our preliminary results revealed neurometabolic changes and suggest a possible prognostic role of the MRS assessment in patients with ET treated by MRgFUS.

Comparative evaluation of tractography-based direct targeting and atlas-based indirect targeting of the ventral intermediate (Vim) nucleus in MRgFUS thalamotomy.

To analyze and compare direct and indirect targeting of the Vim for MRgFUS thalamotomy. We retrospectively evaluated 21 patients who underwent unilateral MRgFUS Vim ablation and required targeting repositioning during the procedures. For each patient, in the three spatial coordinates, we recorded: (i) indirect coordinates; (ii) the coordinates where we clinically observed tremor reduction during the verification stage sonications; (iii) direct coordinates, measured on the dentatorubrothalamic tract (DRTT) at the after postprocessing of DTI data. The agreement between direct and indirect coordinates compared to clinically effective coordinates was evaluated through the Bland-Altman test and intraclass correlation coefficient. The median absolute percentage error was also calculated. Compared to indirect targeting, direct targeting showed inferior error values on the RL and AP coordinates (0.019 vs. 0.079 and 0.207 vs. 0.221, respectively) and higher error values on the SI coordinates (0.263 vs. 0.021). The agreement between measurements was higher for tractography along the AP and SI planes and lower along the RL planes. Indirect atlas-based targeting represents a valid approach for MRgFUS thalamotomy. The direct tractography approach is a valuable aid in assessing the possible deviation of the error in cases where no immediate clinical response is achieved.

Comprehensive Evaluation of Factors Affecting Tremor Relapse after MRgFUS Thalamotomy: A Case-Control Study.

OBJECTIVE: To identify possible relevant factors contributing to tremor relapse after MRgFUS thalamotomy in patients with essential tremor (ET) and Parkinson's disease (PD). METHODS: We identified patients with tremor relapse from a series of 79 treatments in a single institution. The demographic and clinical characteristics of the study group patients were compared to those of patients who did not relapse in the same follow-up period. Imaging and procedural factors were compared using a control group matched for clinical and demographic characteristics. RESULTS: Concerning clinical and demographic characteristics, we did not find statistically significant differences in gender and age. Seventy-three percent of patients with tremor relapse were Parkinson's disease patients. Using MRI, we found larger thalamotomy lesions at the 1-year follow-up in the control group with stable outcomes, compared to patients with tremor relapse. In the tractography evaluation, we found a more frequent eccentric position of the DRTt in patients with tremor relapse. CONCLUSIONS: The most relevant determining factors for tremor relapse after MRgFUS thalamotomy appear to be tremor from Parkinson's disease and inaccurate thalamic targeting. Size of the thalamotomy lesion can also influence the outcome of treatment.

Posterior Reversible Encephalopathy Syndrome Presenting with Atypical Findings: Report of Two Cases.

BACKGROUND: Posterior reversible encephalopathy syndrome (PRES) is characterized by a variable association of symptoms including headache, consciousness impairment, visual disturbances, seizures, and focal neurological signs. Treating the underlying cause usually leads to partial or complete resolution of symptoms within days or weeks. Brain MRI findings include hyperintensities on T2-weighted sequences and their reversibility on follow-up exams. We describe two patients, one with an atypical clinical presentation characterized by a severe and prolonged impairment of consciousness and the other with atypical neuroimaging findings. CASE PRESENTATION: The first patient was a 42-year-old woman, with a negative medical history, presenting with seizures, lethargy, and left hemiparesis, 60 hours after uncomplicated delivery. Brain MRI showed an atypical pattern of alterations, with patchy asymmetric distribution in all lobes. Symptoms completely resolved after twelve days. The second patient was a 59-year-old woman with a history of hypertension, presenting with severe impairment of consciousness, vision loss, and seizures. Symptoms partially resolved after three weeks. CONCLUSION: PRES is characterized by reversible symptoms and radiological findings. Brain MRI usually shows widespread oedema in white matter with typical patterns. The cases we described suggest that PRES may presents with atypical symptoms and radiological manifestations, mimicking other neurological conditions.

Neurological involvement of IgG4-related disease: description of a case and review of the literature.

IgG4-related disease is a recently discovered pathological entity, histologically characterised by fibrosis and IgG4-positive plasma cell infiltration. This condition may virtually involve every site of the organism, with a various range of clinical presentations. The most commonly affected organ is the pancreatic gland, but it can also involve the biliary tract, salivary and lacrimal glands, kidneys, orbital tissues, lymph nodes, lungs and many others. More recently, IgG4-related disease has been demonstrated to involve, in rare cases, also the central nervous system, with a pattern mainly characterised by hypertrophic pachymeningitis. In this paper we evaluated the clinical and magnetic resonance imaging features of the IgG4-related disease in the central nervous system, reporting a case of brain and spinal cord involvement. In our case, in fact, a 62-year-old man complaining of paresthesia, burning dysesthesia and severe hyposthenia in the lower limbs presented with inflammatory pseudotumour with orbital involvement and focal dural and spinal root thickening.