Camilla Russo

Cerebellar lobule atrophy and disability in progressive MS

Objective To investigate global and lobular cerebellar volumetries in patients with progressive multiple sclerosis (MS), testing the contribution of cerebellar lobular atrophy to both motor and cognitive performances. Methods Eighty-two patients with progressive MS and 46 healthy controls (HC) were enrolled in this cross-sectional study. Clinical evaluation included motor and cognitive testing: Expanded Disability Status Scale, cerebellar Functional System score, Timed 25-Foot Walk Test, 9-Hole Peg Test (9-HPT), Symbol Digit Modalities Test (SDMT), Brief Visuospatial Memory Test–Revised (BVMT) and California Verbal Learning Test II (CVLT). Cerebellar volumes were automatically obtained using the Spatially Unbiased Infratentorial Toolbox. A hierarchical multiple linear regression analysis was performed to assess the relationship between MRI variables of supratentorial and cerebellar damage (grey matter fraction, T2 lesion volume, metrics of cerebellar atrophy and cerebellar lesion volume) and motor/cognitive scores. Results Patients with MS exhibited lower cerebellar volumes compared with HC. Regression analysis showed that cerebellar metrics accounted for extra variance in both motor and cognitive performances, with cerebellar lesion volume, cerebellar Lobules VI, Crus I and VIIIa atrophy being independent predictors of 9-HPT, SDMT, BVMT and CVLT performances. Conclusions Atrophy of specific cerebellar lobules explains different aspects of motor and cognitive disability in patients with progressive MS. Investigation of cerebellar involvement provides further insight into the pathophysiological basis of clinical disability in progressive MS.

Motor involvement in Fabry disease

We have read with great interest the article published by Wise and colleagues on the last issue of Molecular Genetics and Metabolism Reports [1]. The Authors performed a survey study investigating the prevalence of Parkinson Disease (PD) in individuals affected by Fabry Disease (FD), and found that 2 patients out of 90 (2.2%) were diagnosed with PD. Although considering all the limitations of their study design, the Authors conclude that there might be an increased risk of developing PD in individuals with α-galactosidase A mutations. The present work is not the first study exploring and suggesting a possible motor involvement in FD. Indeed, as reported in the manuscript, the presence of subtle motor symptoms in FD, with slower gait and transfer speed, poorer fine manual dexterity and lower hand speed, has been reported [2]. In line with these evidences, both electrophysiology and advanced MRI studies showed an involvement of the primary motor cortex in this condition. In particular, with transcranial magnetic stimulation an increase of excitatory neurotransmission in motor cortex circuits of FD patients was found [3], while a reduction of the functional connectivity between motor cortices and both basal ganglia and cerebellum was proved by a resting-state functional MRI study, resembling findings present in early phases of PD [4]. Finally, pathology studies demonstrated the presence of abnormal globotriaosylceramide accumulation in the substantia nigra of FD patients, a central hub of the basal ganglia motor circuit [5]. We think that all these evidences, together with the results of this study, further support the hypothesis of a possible extrapyramidal involvement in FD. However, only future prospective studies, conducted on large samples of FD patients with the integration of different modalities, as well as a direct comparisons between FD and PD patients, can further confirm or dismiss this pathophysiological hypothesis.

Sudden post-traumatic sciatica caused by a thoracic spinal meningioma

Spinal meningiomas usually present with slowly progressive symptoms of cord and root compression, while a sudden clinical onset is very rare. A 35-year-old previously symptom-free woman presented sudden right sciatica and weakness of her right leg following a fall with impact to her left foot. A neurological examination showed paresis of the right quadriceps, tibial and sural muscles, increased bilateral knee and ankle reflexes and positive Babinski sign. Magnetic resonance imaging (MRI) revealed the presence of a spinal T11 meningioma in the left postero-lateral compartment of the spinal canal; at this level, the spinal cord was displaced to the contralateral side with the conus in the normal position. At surgery, a meningioma with dural attachment of the left postero-lateral dural surface was removed. The intervention resulted in rapid remission of both pain and neurological deficits. Spinal meningiomas may exceptionally present with sudden pain and neurological deficits as result of tumour bleeding or post-traumatic injury of the already compressed nervous structures, both in normal patients and in those with conus displacement or tethered cord. In this case, the traumatic impact of the left foot was transmitted to the spine, resulting in stretching of the already compressed cord and of the contralateral lombosacral roots. This case suggests that low thoracic cord compression should be suspected in patients with post-traumatic radicular leg pain with normal lumbar spine MRI.

Striatonigral involvement in Fabry Disease: A quantitative and volumetric Magnetic Resonance Imaging study

INTRODUCTION Aim of this study is to elucidate possible mechanisms of extrapyramidal damage in Fabry Disease (FD), a condition in which involvement of the motor system has been recently suggested, by simultaneously assessing morphometric and susceptibility changes of striatonigral pathway and their possible correlations with clinical variables. METHODS In this cross-sectional study, we investigated possible differences in terms of Quantitative Susceptibility Mapping (QSM) values and volumes of different extrapyramidal relays, including striatum and substantia nigra (SN), in 30 FD patients (M/F = 11/19, mean age 42.6 ± 12.2) and 37 healthy controls (HC) (M/F = 16/21, mean age 43.2 ± 14.6). Patients underwent a clinical examination for the study of different motor functions, and the relationship between MRI and clinical variables was tested using the Spearmans coefficient. RESULTS Compared to HC, FD patients showed an increase in susceptibility values of the SN (p < 0.001) and striatum (p = 0.001), while no difference emerged for the other tested extrapyramidal structures, suggesting their relative sparing. The increased susceptibility was coupled to a reduced volume of the SN (p < 0.001), but not of the striatum (p = 0.34). Finally, no significant correlation emerged when probing the relationship between these modifications and the clinical variables. CONCLUSION In FD patients, susceptibility and volumetric alterations are present throughout the extrapyramidal pathway, with the SN being particularly affected by these changes. Such results are in line with the subtle extrapyramidal involvement recently suggested in FD, and could further contribute to the understanding of the physiopathological bases of cerebral involvement in FD.

Multiple sclerosis and fabry Disease, two sides of the coin? The case of an Italian family

BACKGROUND Multiple Sclerosis (MS) is considered among possible differential diagnosis of Fabry Disease (FD), especially in early stages when findings are suggestive but not diagnostic for MS. We report the case of a family in which FD and MS coexist, offering an overview on clues for differential diagnosis and speculating on shared etiopathogenic mechanisms for these conditions. METHODS Taking as starting point the diagnosis of FD in a dialysis patient during a screening programme, we retrospectively rebuilt his family history and revised clinical and imaging examinations of his five siblings, two of which with previous diagnosis of MS. RESULTS After genetic testing, two subjects were found positive to a new α-galactosidase A mutation, probably causative for FD classical variant. The two subjects meeting diagnostic criteria for MS were found negative to any GLA gene mutation, therefore initial diagnosis was confirmed. The remaining two siblings resulted unaffected, with neither clinical nor instrumental evidence of FD and MS. CONCLUSIONS Differential diagnosis between FD and MS may be challenging, especially in early clinical stages when only extensive clinical evaluation and correct MRI interpretation may reduce the risk of misdiagnosis. Moreover this report allows speculating on potential etiological and pathogenic mechanisms, common both to FD and MS.

Substantia nigra swelling and dentate nucleus T2-hyperintensity may be early MRI signs of BPAN: Early MRI features in four cases of BPAN

Mutations in WDR45 cause β‐propeller protein‐associated neurodegeneration (BPAN), a type of neurodegeneration with brain iron accumulation (NBIA). We reviewed clinical and MRI findings in 4 patients with de novo WDR45 mutations.

Reduced Intracranial Volume in Fabry Disease: Evidence of Abnormal Neurodevelopment?

Introduction: Lysosomal storage disorders (LSD) are often characterized by abnormal brain development, reflected by a reduction of intracranial volume (ICV). The aim of our study was to perform a volumetric analysis of intracranial tissues in Fabry Disease (FD), investigating possible reductions of ICV as a potential expression of abnormal brain development in this condition. Materials and Methods: Forty-two FD patients (15 males, mean age 43.3 ± 13.0 years) were enrolled along with 38 healthy controls (HC) of comparable age and sex. Volumetric MRI data were segmented using SPM12 to obtain intracranial tissue volumes, from which ICV values were derived. Results: Mean ICV of FD patients was 8.1% smaller compared to the control group (p < 5·10−5). Unlike what typically happens in neurodegenerative disorders, no significant differences emerged when comparing between the two groups the fractional volumes of gray matter, white matter and CSF (i.e., normalized by ICV), consistent with a harmonious volumetric reduction of intracranial structures. Discussion: The present results suggest that in FD patients an abnormality of brain development is present, expanding the current knowledge about central nervous system involvement in FD, further emphasizing the importance of an early diagnosis.

Absence of infratentorial lesions in Fabry disease contributes to differential diagnosis with multiple sclerosis

Abstract Background and Purpose Multiple Sclerosis (MS) has been proposed as a possible differential diagnosis with Fabry Disease (FD). We evaluated the incidence of infratentorial lesions in FD patients, investigating whether their presence could help in differentiating these two conditions. We explored the diagnostic accuracy of this sign alone and in combination to the involvement of corpus callosum (CC). Methods White Matter lesions were retrospectively evaluated on FLAIR images available from 136 MS and 144 FD patients. Infratentorial involvement was assessed considering the whole cerebellum, and the part of the brainstem included between the occipital foramen and the upper edge of the red nucleus. Furthermore, the presence of callosal lesions was also recorded, evaluating the portion of CC included between the two external walls of the lateral ventricles. Results Infratentorial involvement was detectable in 119/136 (87.5%) MS patients, while it was present in only 17/144 (11.8%) FD patients. When the diagnostic performance of a positive infratentorial involvement was evaluated in combination with the presence of CC lesions, a specificity of 97%, with a positive predictive value of 96% was reached. Conclusions We concluded that the absence of infratentorial lesions, especially when combined to the evaluation of other typical imaging features, can help in the differential diagnosis between MS and FD.

Cognitive and functional connectivity alterations in Friedreich's ataxia

The aim of this study was to perform the first resting‐state functional MRI (RS‐fMRI) analysis in Friedreichs ataxia (FRDA) patients to assess possible brain functional connectivity (FC) differences in these patients, and test their correlations with neuropsychological performances.

A huge retropharyngeal bronchogenic cyst displacing the posterior wall of the hypopharynx: Case report and review of the literature.

Lesions of the retropharyngeal space (RPS) are uncommon, and they generally present as solitary, painless masses, which are often cystic. They usually originate from branchial arches anomalies, and only in a few cases do they turn out to be bronchogenic cysts. Generally, these lesions are diagnosed in childhood, but sometimes they can appear in adulthood. We report here a rare case of a bronchogenic cyst expanding into the RPS and causing dysphagia in an adult patient treated surgically. Since the RPS is clinically inaccessible, clinical examination was not crucial in determining the correct diagnosis, and only the additional information provided by radiological examinations led to the final diagnosis, which is essential for accurate surgical planning.