Multifaceted superoxide dismutase 1 expression in amyotrophic lateral sclerosis patients: a rare occurrence?

Amyotrophic lateral sclerosis (ALS) is a neuromuscular condition resulting from the progressive degeneration of motor neurons in the cortex, brainstem, and spinal cord. While the typical clinical phenotype of ALS involves both upper and lower motor neurons, human and animal studies over the years have highlighted the potential spread to other motor and non-motor regions, expanding the phenotype of ALS. Although superoxide dismutase 1 (SOD1) mutations represent a minority of ALS cases, the SOD1 gene remains a milestone in ALS research as it represents the first genetic target for personalized therapies. Despite numerous single case reports or case series exhibiting extramotor symptoms in patients with ALS mutations in SOD1 (SOD1-ALS), no studies have comprehensively explored the full spectrum of extramotor neurological manifestations in this subpopulation. In this narrative review, we analyze and discuss the available literature on extrapyramidal and non-motor features during SOD1-ALS. The multifaceted expression of SOD1 could deepen our understanding of the pathogenic mechanisms, pointing towards a multidisciplinary approach for affected patients in light of new therapeutic strategies for SOD1-ALS.

Exploring therapeutic interventions for functional neurological disorders: a comprehensive scoping review.

Functional Neurological Disorders (FNDs) are characterized by the symptoms experienced by the individuals but also by how they express personal experiences and concerns related to the clinical condition. Access to care programs for functional neurological symptoms appears challenging and may entail circular, self-perpetuating healthcare pathways. Given the challenging and misleading interpretations around FND, in advocating for care pathways beyond medical therapies, we designed a scoping review to map recently suggested practices and interventions. We identified 31 relevant papers published between January 2018 and December 2022. Most of the literature was gathered from the US and UK healthcare experiences, with documented interventions provided by multi-professional teams or stand-alone psychotherapists. We found different care pathways addressing either motor or non-motor manifestations. Persons with Functional Motor Disorder are more likely to be referred to physical therapy first, while Persons suffering from Non-Epileptic Seizures are to mental health services. A narrow focus was given to minor components of multimodal approaches (e.g. social workers, and occupational therapists). High heterogeneity was found between assessment instruments as well, reflecting different perspectives in selecting treatment outcomes (e.g., reduction of non-epileptic events, psychological functioning, motor symptoms). Among healthcare professionals, neurologists and (neuro)psychiatrists are typically engaged in formulating and delivering diagnoses, while treatment is often administered by physiotherapists and/or psychologists. In the context of FNDs, the complex etiopathological nature of the condition, including comorbidities, suggests the recommendation of multidisciplinary treatments adopting a stepped care model progressing from standard to higher level individualized modules may better suit individual complexities.

Cerebellar mutism syndrome caused by bilateral cerebellar hemorrhage in adults: a case report and review of the literature.

Cerebellar mutism syndrome (CMS) is a frequent complication of surgical intervention on posterior fossa in children. It has been only occasionally reported in adults and its features have not been fully characterized. In children and in young adults, medulloblastoma is the main reason for neurosurgery. A single case of postsurgical CMS is presented in an adult patient with a cerebellar hemorrhage and a systematic review of the published individual cases of CMS in adults was done. Literature review of individual cases found 30 patients, 18/30 (60%) males, from 20 to 71 years at diagnosis. All but one case was post-surgical, but in one of the post-surgical cases iatrogenic basilar artery occlusion was proposed as cause for CMS. The causes were: primary tumors of the posterior fossa in 16/22 (72.7%) metastasis in 3/30 (10%), ischemia in 3/30 (10%) cerebellar hemorrhage in 3/30 (10%), and benign lesions in 2/30 (6.7%) patients. 8/30 patients (26.7%) were reported as having persistent or incomplete resolution of CMS within 12 months. CMS is a rare occurrence in adults and spontaneous cerebellar hemorrhage has been reported in 3/30 (10%) adult patients. The generally accepted hypothesis is that CMS results from bilateral damage to the dentate nucleus or the dentate-rubro-thalamic tract, leading to cerebro-cerebellar diaschisis. Several causes might contribute in adults. The prognosis of CMS is slightly worse in adults than in children, but two thirds of cases show a complete resolution within 6 months.

Persistent intracranial steno-occlusion from calcified embolism: a treatment challenge.

INTRODUCTION: Calcified arterial cerebral embolism is a rare occurrence among large and medium vessel occlusions causing ischemic stroke and its diagnosis and treatment is a challenge. The sources of calcified embolism might be a calcific atheroma from the aortic arch and carotid artery, but also heart valve disease has been reported in the literature. Calcified embolism is frequently simultaneous on multiple vascular territories. The prognosis of patients is usually poor, including patients treated by using endovascular thrombectomy (EVT) and this diagnosis could be easily missed in the acute phase. In addition, the optimal secondary prevention has not been yet fully stated. METHODS: We are presenting two cases of acute stroke due to calcified embolism in the middle cerebral artery (MCA) coming from a complicated carotid atheroma, non-stenosing in the first case (a 49 years old man) and stenosing in the second case (a 71 years old man) without clinical indications to intravenous thrombolysis and/or EVT, extensively investigated in the acute phase and followed-up for over 12 months with a favorable clinical course and the persisting steno-occlusion in the involved MCA. In both cases, antiplatelet treatment and targeting of vascular risk factors were done without recurrences in the follow-up period. DISCUSSION: Cerebral calcified embolism has been reported in 5.9% of cases of acute ischemic stroke in a single center series and only in 1.2% of a large retrospective cohort of EVT-treated patients. In both series the prognosis was poor and only one third of EVT-treated patients had functional independence at 3-months follow-up. The natural history of these subtype of ischemic stroke is relatively poorly understood and both etiological diagnosis and treatment have not yet defined. It is possible that some cases might be underdiagnosed and underreported. CONCLUSIONS: Calcified cerebral embolism is a rare cause of stroke, but it is largely underreported and both acute phase and secondary preventive treatment have to be defined.

Stroke-Induced Secondary Neurodegeneration of the Corticospinal Tract-Time Course and Mechanisms Underlying Signal Changes in Conventional and Advanced Magnetic Resonance Imaging.

Secondary neurodegeneration refers to the final result of several simultaneous and sequential mechanisms leading to the loss of substance and function in brain regions connected to the site of a primary injury. Stroke is one of the most frequent primary injuries. Among the subtypes of post-stroke secondary neurodegeneration, axonal degeneration of the corticospinal tract, also known as Wallerian degeneration, is the most known, and it directly impacts motor functions, which is crucial for the motor outcome. The timing of its appearance in imaging studies is usually considered late (over 4 weeks), but some diffusion-based magnetic resonance imaging (MRI) techniques, as diffusion tensor imaging (DTI), might show alterations as early as within 7 days from the stroke. The different sequential pathological stages of secondary neurodegeneration provide an interpretation of the signal changes seen by MRI in accordance with the underlying mechanisms of axonal necrosis and repair. Depending on the employed MRI technique and on the timing of imaging, different rates and thresholds of Wallerian degeneration have been provided in the literature. In fact, three main pathological stages of Wallerian degeneration are recognizable-acute, subacute and chronic-and MRI might show different changes: respectively, hyperintensity on T2-weighted sequences with corresponding diffusion restriction (14-20 days after the injury), followed by transient hypointensity of the tract on T2-weighted sequences, and by hyperintensity and atrophy of the tract on T2-weighted sequences. This is the main reason why this review is focused on MRI signal changes underlying Wallerian degeneration. The identification of secondary neurodegeneration, and in particular Wallerian degeneration, has been proposed as a prognostic indicator for motor outcome after stroke. In this review, the main mechanisms and neuroimaging features of Wallerian degeneration in adults are addressed, focusing on the time and mechanisms of tissue damage underlying the signal changes in MRI.

The Prepetrous Segment of the Internal Carotid Artery as a Neglected Site of Symptomatic Atherosclerosis: A Single-Center Series.

(1) Background: Non-stenotic complicated plaques are a neglected cause of stroke, in particular in young patients. Atherosclerosis has some preferential sites in extracranial arteries and the prepetrous segment of the internal carotid artery has been rarely described as site of atheroma in general and of complicated atheroma in stroke patients. The aim of this study is to describe the rate of the prepetrous internal carotid artery's (ICA) involvement in a single-center case series of young stroke patients. (2) Methods: All patients < 50 years old with acute ischemic stroke admitted to a single-center Stroke Unit during two time periods (the first one from 1 January 2018 to 31 December 2019, and the second one from 1 January 2021 to 30 June 2022), were prospectively investigated as part of a screening protocol of the Searching for Explanations for Cryptogenic Stroke in the Young: Revealing the Etiology, Triggers, and Outcome (SECRETO) study [ClinicalTrials.gov ID NCT01934725], including extracranial vascular examination by using computed tomography (CT) or magnetic resonance imaging (MRI). (3) Results: Two out of ninety-three consecutive patients (2.15%) had a complicated atheroma in the prepetrous ICA as the cause of stroke and both CT angiography and high-resolution vessel wall MRI were applied to document the main features of positive remodeling, cap rupture, ulceration, intraplaque hemorrhage, and a transient thrombus superimposed on the atheroma. The two patients had a different evolution of healing in the first case and a persisting ulceration at 12 months in the second case. (4) Conclusions: The prepetrous ICA is a rarely described location of complicated atheroma in stroke patients at all ages and it represents roughly 2% of causes of acute stroke in this single-center case series in young people.

Tumor-like Lesions in Primary Angiitis of the Central Nervous System: The Role of Magnetic Resonance Imaging in Differential Diagnosis.

Primary Angiitis of the Central Nervous System (PACNS) is a rare disease and its diagnosis is a challenge for several reasons, including the lack of specificity of the main findings highlighted in the current diagnostic criteria. Among the neuroimaging pattern of PACNS, a tumefactive form (t-PACNS) is a rare subtype and its differential diagnosis mainly relies on neuroimaging. Tumor-like mass lesions in the brain are a heterogeneous category including tumors (in particular, primary brain tumors such as glial tumors and lymphoma), inflammatory (e.g., t-PACNS, tumefactive demyelinating lesions, and neurosarcoidosis), and infectious diseases (e.g., neurotoxoplasmosis). In this review, the main features of t-PACNS are addressed and the main differential diagnoses from a neuroimaging perspective (mainly Magnetic Resonance Imaging-MRI-techniques) are described, including conventional and advanced MRI.

The Hemorrhagic Side of Primary Angiitis of the Central Nervous System (PACNS).

Primary Angiitis of the Central Nervous System (PACNS) is a rare cerebrovascular disease involving the arteries of the leptomeninges, brain and spinal cord. Its diagnosis can be challenging, and the current diagnostic criteria show several limitations. Among the clinical and neuroimaging manifestations of PACNS, intracranial bleeding, particularly intracerebral hemorrhage (ICH), is poorly described in the available literature, and it is considered infrequent. This review aims to summarize the available data addressing this issue with a dedicated focus on the clinical, neuroradiological and neuropathological perspectives. Moreover, the limitations of the actual data and the unanswered questions about hemorrhagic PACNS are addressed from a double point of view (PACNS subtyping and ICH etiology). Fewer than 20% of patients diagnosed as PACNS had an ICH during the course of the disease, and in cases where ICH was reported, it usually did not occur at presentation. As trigger factors, both sympathomimetic drugs and illicit drugs have been proposed, under the hypothesis of an inflammatory response due to vasoconstriction in the distal cerebral arteries. Most neuroradiological descriptions documented a lobar location, and both the large-vessel PACNS (LV-PACNS) and small-vessel PACNS (SV-PACNS) subtypes might be the underlying associated phenotypes. Surprisingly, amyloid beta deposition was not associated with ICH when histopathology was available. Moreover, PACNS is not explicitly included in the etiological classification of spontaneous ICH. This issue has received little attention in the past, and it could be addressed in future prospective studies.

Caregivers' burden and deep brain stimulation for Parkinson disease: A systematic review of qualitative studies.

BACKGROUND AND PURPOSE: The impact of subthalamic nucleus deep brain stimulation (STN-DBS) on caregivers' burden is understudied. We perform a systematic review and meta-synthesis aggregating qualitative studies involving partners of people with Parkinson disease (PwP) to explore their experiences and unmet needs. METHODS: A systematic review for retrieving qualitative studies included six databases: MEDLINE, Embase, CINAHL, Cochrane, PsycInfo, and Scopus. Inclusion criteria were as follows: (i) studies on the experience of caregivers of PwP in the context of STN-DBS, (ii) English peer-reviewed articles, and (iii) qualitative or mixed methods studies reporting caregivers' quotations. After the appraisal of included studies, we performed meta-synthesis of qualitative findings. Descriptive themes and conceptual elements related to PwP partners' experiences and unmet needs were generated. RESULTS: A total of 1108 articles were screened, and nine articles were included. Three categories were identified: (i) dealing with Parkinson disease (PD) every day (the starting situation characterized by the impact of PD on ordinary life; the limitations to partners' socialization; partners' efforts in stepping aside for love and care activities), (ii) facing life changes with STN-DBS (the feeling of being unprepared for changes; the fear and concern due to loved ones' behavioral changes; struggling to find an explanation for those changes), and (iii) rebuilding the role of caregiver and partner after STN-DBS. CONCLUSIONS: This meta-synthesis elucidates concerns, challenges, and unmet needs of partners of PwP who underwent STN-DBS. It is important to provide them with information, education, and adequate support to face these challenges. Professionals need to involve partners in the care and decision process, because STN-DBS-related outcomes do not depend solely on the well-being of PwP but also on the well-being of individuals surrounding them.

Twig-like Middle Cerebral Artery: Case Series in a European Population.

OBJECTIVES: Twig-like middle cerebral artery (MCA) is a rare anomaly where the M1 MCA is partially or completely replaced by a plexiform network. It has been described in angiographic series from Asian and South-American cohorts, but has not yet been reported in a European population. METHODS: The digital subtraction angiograms (DSAs) of adult patients referred to a single neurovascular center for a diagnostic hypothesis of moyamoya arteriopathy (MMA) from 2018 to 2023 were prospectively and retrospectively checked by experienced neuroradiologists for identifying patients with twig-like MCA. The angioarchitecture of twig-like MCA was systematically evaluated and described. RESULTS: Five of 30 (16.7%) male patients (mean age 55.8 + 14.7 years) of European ancestry were identified as having twig-like MCA. The clinical presentations were ischemic stroke (2 of 5), hemorrhagic stroke (1 of 5), and headache (2 of 5). All patients showed a unilateral involvement on DSA and in 1 of 5 (20%) an intracranial aneurysm was found. DSA was used to confirm the diagnosis of twig-like MCA and define the angioarchitecture and associated anomalies. An accessory MCA and recurrent artery of Heubner were found in 3 of 5 (60%) cases, feeding the network together with the anterior choroidal artery (4 of 5, 80%). CONCLUSIONS: Twig-like MCA is a rare vascular anomaly, but it seems to be less rare than expected among adult European patients with suspected MMA on noninvasive neuroimaging studies. DSA is fundamental for a reliable differential diagnosis and should not be omitted in these patients.

Olfactory status in neurodegeneration with brain iron accumulation disorders.

BACKGROUND: Olfactory dysfunction has been suggested as a diagnostic and discriminative biomarker in some neurodegenerative disorders. However, there are few studies regarding the olfactory status in rare diseases including neurodegeneration with brain iron accumulation (NBIA) disorders. METHODS: Genetically-confirmed NBIA patients were enrolled. Neurological and cognitive examinations were conducted according to the Pantothenate Kinase-Associated Neurodegeneration-Disease Rating Scale (PKAN-DRS) and the Mini-Mental State Examination (MMSE) questionnaire, respectively. Olfaction was assessed in three domains of odor threshold (OT), odor discrimination (OD), odor identification (OI), and total sum (TDI) score by the Sniffin' Sticks test. The olfactory scores were compared to a control group and a normative data set. RESULTS: Thirty-seven patients, including 22 PKAN, 6 Kufor Rakeb syndrome, 4 Mitochondrial membrane Protein-Associated Neurodegeneration (MPAN), 5 cases of other 4 subtypes, and 37 controls were enrolled. The mean PKAN-DRS score was 51.83±24.93. Sixteen patients (55.2%) had normal cognition based on MMSE. NBIA patients had significantly lower olfactory scores compared to the controls in TDI and all three subtests, and 60% of them were hyposmic according to the normative data. Including only the cognitively-normal patients, still, OI and TDI scores were significantly lower compared to the controls. The phospholipase A2-Associated Neurodegeneration (PLAN) and MPAN patients had a significantly lower OI score compared to the cognitively-matched PKAN patients. CONCLUSION: Olfactory impairment as a common finding in various subtypes of NBIA disorder can potentially be considered a discriminative biomarker. Better OI in PKAN compared to PLAN and MPAN patients may be related to the different underlying pathologies.

Implantable SDF-1α-loaded silk fibroin hyaluronic acid aerogel sponges as an instructive component of the glioblastoma ecosystem: Between chemoattraction and tumor shaping into resection cavities.

In view of inevitable recurrences despite resection, glioblastoma (GB) is still an unmet clinical need. Dealing with the stromal-cell derived factor 1-alpha (SDF-1α)/CXCR4 axis as a hallmark of infiltrative GB tumors and with the resection cavity situation, the present study described the effects and relevance of a new engineered micro-nanostructured SF-HA-Hep aerogel sponges, made of silk fibroin (SF), hyaluronic acid (HA) and heparin (Hep) and loaded with SDF-1α, to interfere with the GB ecosystem and residual GB cells, attracting and confining them in a controlled area before elimination. 70 µm-pore sponges were designed as an implantable scaffold to trap GB cells. They presented shape memory and fit brain cavities. Histological results after implantation in brain immunocompetent Fischer rats revealed that SF-HA-Hep sponges are well tolerated for more than 3 months while moderately and reversibly colonized by immuno-inflammatory cells. The use of human U87MG GB cells overexpressing the CXCR4 receptor (U87MG-CXCR4+) and responding to SDF-1α allowed demonstrating directional GB cell attraction and colonization of the device in vitro and in vivo in orthotopic resection cavities in Nude rats. Not modifying global survival, aerogel sponge implantation strongly shaped U87MG-CXCR4+ tumors in cavities in contrast to random infiltrative growth in controls. Overall, those results support the interest of SF-HA-Hep sponges as modifiers of the GB ecosystem dynamics acting as "cell meeting rooms" and biocompatible niches whose properties deserve to be considered toward the development of new clinical procedures. STATEMENT OF SIGNIFICANCE: Brain tumor glioblastoma (GB) is one of the worst unmet clinical needs. To prevent the relapse in the resection cavity situation, new implantable biopolymer aerogel sponges loaded with a chemoattractant molecule were designed and preclinically tested as a prototype targeting the interaction between the initial tumor location and its attraction by the peritumoral environment. While not modifying global survival, biocompatible SDF1-loaded hyaluronic acid and silk fibroin sponges induce directional GB cell attraction and colonization in vitro and in rats in vivo. Interestingly, they strongly shaped GB tumors in contrast to random infiltrative growth in controls. These results provide original findings on application of exogenous engineered niches that shape tumors and serve as cell meeting rooms for further clinical developments.

Posterior reversible encephalopathy syndrome and acute ischemic stroke: an underreported association.

INTRODUCTION: Posterior reversible encephalopathy syndrome (PRES) is a rare and complex disorder with variable clinical presentation and a typical magnetic resonance imaging (MRI) pattern of vasogenic edema with typical and atypical locations. It is often triggered by other diseases and drugs and the most prototypical association is with persistently elevated arterial pressure values. Among the potential cerebrovascular complications, intracranial bleeding has been described, but ischemic stroke is uncommonly reported. METHODS: We are presenting a case of a male patient with prolonged and sustained arterial hypertension acutely presenting with lacunar ischemic stroke involving the right corona radiata and composite MRI findings with the association of chronic small vessel disease (SVD) markers, acute symptomatic lacunar stroke, and atypical, central variant, posterior fossa dominant PRES. In the MRI follow-up, the white matter hyperintensities in T2-fluid attenuated inversion recovery (FLAIR sequences) due to PRES. DISCUSSION: The pathophysiology of PRES is not yet fully known, but the association with markedly increased values of arterial pressure is typical. In this context, ischemic stroke has not been considered in the clinical and neuroradiological manifestations of PRES and it has been only occasionally reported in the literature. In this case, the main hypothesis is that sustained hypertension may have triggered both manifestations, PRES, and ischemic stroke and the last one allowed to diagnose the first one. CONCLUSIONS: Atypical variants of PRES are not so rare and it may also occur in typical triggering situations. The association with ischemic stroke is even rarer and it may add some clues to the pathomechanisms of PRES.

Are patients with GBA-Parkinson disease good candidates for deep brain stimulation? A longitudinal multicentric study on a large Italian cohort.

BACKGROUND: GBA variants increase the risk of developing Parkinson disease (PD) and influence its outcome. Deep brain stimulation (DBS) is a recognised therapeutic option for advanced PD. Data on DBS long-term outcome in GBA carriers are scarce. OBJECTIVE: To elucidate the impact of GBA variants on long-term DBS outcome in a large Italian cohort. METHODS: We retrospectively recruited a multicentric Italian DBS-PD cohort and assessed: (1) GBA prevalence; (2) pre-DBS clinical features; and (3) outcomes of motor, cognitive and other non-motor features up to 5 years post-DBS. RESULTS: We included 365 patients with PD, of whom 73 (20%) carried GBA variants. 5-year follow-up data were available for 173 PD, including 32 mutated subjects. GBA-PD had an earlier onset and were younger at DBS than non-GBA-PD. They also had shorter disease duration, higher occurrence of dyskinesias and orthostatic hypotension symptoms.At post-DBS, both groups showed marked motor improvement, a significant reduction of fluctuations, dyskinesias and impulsive-compulsive disorders (ICD) and low occurrence of most complications. Only cognitive scores worsened significantly faster in GBA-PD after 3 years. Overt dementia was diagnosed in 11% non-GBA-PD and 25% GBA-PD at 5-year follow-up. CONCLUSIONS: Evaluation of long-term impact of GBA variants in a large Italian DBS-PD cohort supported the role of DBS surgery as a valid therapeutic strategy in GBA-PD, with long-term benefit on motor performance and ICD. Despite the selective worsening of cognitive scores since 3 years post-DBS, the majority of GBA-PD had not developed dementia at 5-year follow-up.

Predictors of respiratory failure in Guillain-Barré syndrome: a 22 year cohort study from a single Italian centre.

BACKGROUND AND PURPOSE: The study aimed to identify predictors of respiratory failure leading to mechanical ventilation (MV) and tracheostomy in Guillain-Barré syndrome (GBS). METHODS: Two hundred and thirty adult cases admitted to the Neurology Unit of Modena, Italy, between January 2000 and December 2021 were studied. A cut-off of MV starting within 8 weeks from onset of weakness was used. Univariable, multivariable logistic and Cox regression analyses were used to determine which pre-specified clinical and diagnostic characteristics were capable of predicting MV and tracheostomy, due to weaning failure. The model was internally validated within the full cohort. The Erasmus GBS Respiratory Insufficiency Score was retrospectively applied. RESULTS: One hundred and seventy-six cases (76.5%) were classified as classical sensorimotor GBS and 54 (23.4%) as variants. Thirty-two patients (13.9%) needed MV: 84.3% required respiratory support within 7 days. Independent predictors of respiratory failure and MV were older age, facial, bulbar, neck flexor weakness, dysautonomia, axonal electrophysiological subtype, cardiovascular comorbidities and higher disability score at entry. There was no association with abnormal spinal fluid parameters nor with positive serology for recent infections. Twenty-two patients (68.7%) were ventilated for more than 7 days; 4.7% died within 8 weeks. The patients who required MV were treated more often with plasma exchange. Independent predictors of tracheostomy due to weaning trial failure were facial, bulbar, neck flexor weakness, autonomic dysfunction, associated cardiovascular morbidities and axonal electrophysiological subtype on nerve conduction study. CONCLUSIONS: Our study indicates distinct predictors of MV and tracheostomy in GBS patients.

Vestibular Hypofunction in ARSACS Syndrome: A Possible Pitfall in the Differential Diagnosis of Recessive Cerebellar and Afferent Ataxias.

Objectives: Autosomal recessive spastic ataxia of Charlevoix-Saguenay (ARSACS) is an early-onset ataxia characterized by cerebellar dysfunction, spasticity, and sensory-motor polyneuropathy due to variations in the SACS gene (13q11). To date, no studies have instrumentally assessed vestibular function in this condition. Methods: We report a 36-year-old woman with diagnosis of ARSACS syndrome due to homozygous mutation (c.12232 C>T, p.Arg4078Ter) in the SACS gene. Neurologic examination showed spastic-ataxic gait, dysarthric speech, 4-limb ataxia, and spastic hypertonia with lower limb hyperreflexia. Results: A vestibular instrumental evaluation including bedside oculomotor testing found gaze-evoked and rebound nystagmus on horizontal and vertical gaze, saccadic movements within normality ranges, saccadic pursuit, and slightly impaired visually enhanced vestibulo-ocular reflex (VVOR). A near-normal VOR suppression (VORS) was recorded. Neither head shakings, skull vibrations, nor supine positionings could evoke nystagmus. Finally, the video-head impulse test detected a symmetrical VOR impairment for all the semicircular canals (SCs), mostly involving the horizontal SCs, with corrective saccades in all planes. Discussion: Vestibular hypofunction may be found in ARSACS syndrome and may represent a possible pitfall in the differential diagnosis of recessive cerebellar and afferent ataxias. In this setting, ARSACS syndrome should be considered in the differential diagnosis of CANVAS.

"Somewhere Between an Actual Disease and a Disease": A Grounded Theory Study on Diagnosing Functional Neurological Disorders From a Multi-Informant Perspective.

Functional Neurological Disorders are characterized by sensory-motor or cognitive symptoms. Recent research has revealed their complex nature involving biological, psychological, and social factors. Care requires a multidisciplinary approach, which, to date, has yet to be considered. A Constructivist Grounded Theory study was conducted to understand the reasons behind this, exploring Functional Neurological Disorders diagnosis, communication, and understanding from multiple perspectives (patients and healthcare professionals). The core category was "negotiating Functional Neurological Disorders meanings and care amid a dissatisfying dichotomy," with sub-categories: i) seeking to "word" the disease, ii) exposing reductionism, and iii) a pluralist vision emerging. Diagnosing and communicating Functional Neurological Disorders is a process of negotiating meanings and care that hinges on participants' diverse ontological perspectives regarding the condition. Results highlight the difficulty in finding common ground and achieving mutual understanding among the various viewpoints, creating a challenge in establishing a unified approach to Functional Neurological Disorders care. In this context, only a few healthcare professionals emphasized the potential benefits of increased integration. A shift is required from a reductionist to an integrated biopsychosocial perspective to develop a more cohesive approach. Defining a medical paradigm through dialogue with teams and patients is essential in addressing Functional Neurological Disorders effectively. Furthermore, the required interdisciplinary approach holds the potential to mitigate the dissatisfaction arising from fragmented and compartmentalized care (the "dissatisfying dichotomy") experienced by our participants. It signifies a comprehensive strategy that could address the concerns of all involved parties and enhance the overall quality of care provided.