Presence Of Neurological Involvement Research Articles

MO028: Kidney biopsy in females with Fabry disease is an important tool to establish the indication for Fabry-specific therapy

Abstract BACKGROUND AND AIMS Fabry disease (FD) is a rare lysosomal storage disease causing progressive kidney, nervous system and heart disorders. Specific therapy may stop or mitigate disease progression, but is very expensive and results depend significantly on early initiation of treatment. Thus, clear criteria for treatment options are necessary. Kidney biopsy in FD has important diagnostic, prognostic and therapeutically implications. Some countries already decided to include as a criterion for reimbursement of FD-specific therapy in presence of renal biopsy evidence related to FD. National criteria for starting FD specific therapy according to renal involvement include eGFR <80 mL/min/1.73 m2 and/or proteinuria >300 mg/day. METHOD The aim of our retrospective study is to evaluate clinical and histological aspects of renal involvement in untreated female patients diagnosed with FD by genetic test between 2015 and 2021 in our center. Biological renal manifestations using serum creatinine, albumin creatinine ratio and proteinuria. Also, presence of neurological involvement was assessed by clinical exam, electroneurographic exam and brain magnetic resonance, and heart manifestations were assessed by echocardiography, electrocardiogram (ECG), ECG Holter and cardiac magnetic resonance. Kidney biopsy specimens were analyzed by light and electron microscopy. Specific renal FD lesions, as well as general lesions of progression, were evaluated according to the International Study Group of Fabry Nephropathy Score Sheet. RESULTS From a total of 25 female patients, we enrolled 11 female patients in which kidney biopsy was performed. The mean age at diagnosis was 47.7 ± 12 years (range 30–65 years), although mean age of symptoms onset was 36.1 years. The mean eGFR was 72.7 ± 19.8 mL/min/1.72 m2 while mean proteinuria was 0.72 ± 1.3 mg/day. Average Mainz score was 16.6 ± 11.5. Heart involvement was found in five patients (45.5%), and neurological manifestations were present in five patients. Co-morbidities were as follows: arterial hypertension in six patients, diabetes mellitus in one patient and obesity in two patients. All kidney biopsies showed lysosomal accumulation in the podocytes, in the parietal cells of the Bowman capsule and in the tubules, while vascular inclusions were found in nine cases. Also, we observed segmental glomerular sclerosis in four cases and global glomerular sclerosis in three cases, interstitial fibrosis in six cases, tubular atrophy in five cases, arteriosclerosis in four cases and arteriolar hyalinosis in five cases. Considering national criteria for initiation of FD therapy, five patients (54.6%) fulfilled the renal criteria, three patients (27.3%) presented criteria for other organs involvement, while three patients (mean age 37.7 years) did not fulfill any criteria. We emphasize that, even in our six patients without renal criteria for FD therapy, kidney biopsy showed FD-specific lesions (lysosomal accumulation) in all cases, associated with segmental glomerular sclerosis in one case, interstitial fibrosis in four cases, tubular atrophy in three cases, arteriosclerosis in one case and arteriolar hyalinosis in three cases. Thus, in our three patients without clinical, biological and imaging criteria for FD therapy, evidence of specific FD lesions in kidney biopsy supported our recommendation to initiate FD treatment. CONCLUSION The data from our small cohort of females with Fabry disease underline the importance of kidney biopsy for detection of early kidney involvement and provide additional support to the consideration of early initiation of FD-specific therapy, potentially improving long-term outcome. Thus, proof of specific FD renal lesions as revealed by kidney biopsy could become a distinct criterion for initiation of FD therapy, in the absence of other criteria according to current guidelines. Future studies are necessary in order to specify the role of renal histology in the establishment of the proper timing to start the FD treatment, especially in young patients.

Traumatic Spinal Injuries in Saudi Arabia: A Retrospective Single-center Medical Record Review

Introduction: The aim of this retrospective medical record review was to describe the patterns and outcomes of traumatic spinal injuries (TSIs) in a tertiary care trauma center in Riyadh, Saudi Arabia.
 Methodology: Data of all patients who presented at a setting level-1 trauma center with any type of spinal trauma between February 1, 2016 and December 31, 2018 were review. The data obtained included age, gender, nationality (as Saudi and non-Saudi), date of presentation, site of fracture/injury, associated injuries, mechanism of injury, presence of neurological involvement, and hospital mortality. The main outcome of the review was frequencies of different types of TSI across various subgroups.
 Result: We identified 692 patients who presented with TSI during the study period. The mean age was 36.9 years. Males represented 83.2% (n = 576) of the sample size, and the most common mechanism of injury was motor vehicle collision (MVC), accounting for 66.8% of the cases (n = 462), while fall-related injuries were seen in 31.6% of the cases (n = 219). A total of 454 (65.6%) of all patients were Saudi, and 332 (73.1%) of the TSIs in Saudis were due to MVC. Non-Saudi cases accounted for 238 (34.4%) of all patients, and 89 (37.4%) of the non-Saudi injuries were due to falls from height, this association was statistically significant (p < 0.001).
 Conclusion: TSI was not thoroughly examined in Saudi Arabia; therefore, this study is considered the first to be done in the Kingdom using a representative sample. The fact that non-Saudi patients had a higher proportion of falls as a mechanism of injury should be taken into consideration in terms of raising awareness and taking more safety precautions, as most construction workers tend to be expatriates.

Traumatic spinal injuries in Saudi Arabia: a retrospective single-centre medical record review

ObjectivesTo describe the patterns and outcomes of traumatic spinal injuries (TSIs) in a tertiary care trauma centre in Riyadh, Saudi Arabia.DesignRetrospective medical record review.SettingLevel 1 trauma centre for all patients...

Surgical management of a combined fracture of the odontoid process with an atlas posterior arch disruption: A review of four cases

Four cases of operated odontoid process fractures associated with a fracture of the posterior arch of the atlas are presented. Three types of surgery were performed: atlas-axis fusion, occipitocervical fusion, and odontoid process screw fixation. Based on a literature review and our experience, the therapeutic management is discussed according to the type of odontoid fracture and the presence of neurological involvement, with a reminder that wiring is not indicated when C1 posterior arch continuity is compromised.

Maladie de Gaucher : particularités cliniques chez l’enfant: Gaucher disease in childhood

Gaucher disease is well-known in adult patients and must be regarded as a pædiatric disease, two thirds of the patients manifesting before the age of 20. Three clinical forms have been defined based on the presence of neurological involvement. Gaucher disease type 1, without neurological signs, generally begins before the five years age with splenomegaly as the main symptom. The bone crises are more frequent than in adulthood. Gaucher disease type 2 or acute neuronopathic form begins between three and six months and do not have any treatment. Type 3 or chronic neuronopathic form appears like a type 1 with progressive horizontal saccade-initiation failure and developmental delay. Onset in childhood is predictive of a severe and progressive phenotype. The presence of neurological symptoms induces important consequences for treatment, prognosis and genetic counselling.

Definite multiple sclerosis and uveitis: a two cases report

Uveitis has infrequently been described as a manifestation of ocular inflammation in patients with multiple sclerosis (MS). Two patients with pre-existing definite MS and uveitis were described. The first patient had features of intermediate uveitis, and the second case had a features of retinal periphlebitis. However, each patient had neurologic signs consistent with MS and a negative laboratory tests for inflammatory and infectious diseases. The presence of neurological involvement with uveitis need a sequential diagnostic search.

Antibodies to gangliosides in coeliac disease with neurological manifestations

Sirs, The authors thank Dr Volta et al. for their interest in our article on ‘Antiganglioside antibodies in children with celiac disease’,1 and for calling attention to their interesting data on adult coeliac disease (CD) patients with and without neurological manifestations. The authors find antibodies to GM1 and GD1b gangliosides in 36% of CD patients with neurological manifestations compared with 10% of CD patients without neurological symptoms. Although the difference is not significant, it points to a greater level of autoimmunity to neuronal antigens in CD patients with neurological manifestations. Different biological and immunological characteristics in childhood and adulthood, make it difficult to compare our findings in CD children to those reported in adults, as was discussed in our paper.1 Children express higher IgM antiganglioside antibody levels in the absence of neurological symptoms, whereas some CD adults with neuropathy have IgG antibodies to gangliosides.2 It would be interesting to know the antibody isotype for the CD patients described by Dr Volta et al. The different isotype may, in fact, reflect a different function of the antibodies (expression of innate repertoire in children, possible T cell-mediated mechanism of pathogenicity in adults), thus explaining the absence or presence of neurological involvement. The authors agree with Dr Volta et al. that the difference between the two studies might be ascribed to the well-known higher prevalence of neurological complications in adult, although it is still unclear whether this is a consequence of a longer exposure to gluten. We are currently prospectively following 42 adults with CD (32 female, 10 males, median age 36.3 ± 12 years), four of whom (9.5%) have clinical and neurophysiological evidence of mild, often subclinical, neuropathy.3 However, antiganglioside antibodies are not present in this population. It is possible that a more severe nerve damage is required before the antiganglioside antibodies are generated as a secondary response. Interestingly, three of the four patients with neuropathy have been on gluten-free diet for several years (11, 6, and 2, respectively), thus likely excluding a direct role of gluten in nerve damage. On the contrary, five of the 42 patients had antiganglioside antibody titres in the absence of neurological symptoms or signs. A follow-up evaluation after a median period of 9 months of both neurophysiological and humoral parameters did not show any significant difference. Hopefully, a large-scale prospective study might help to define the role, if any, of the antibodies to neuronal antigens in the neurological complications of CD.

Transcranial Doppler detection of microembolic signals in patients with Behçet's disease

We evaluated the prevalence of microembolic signals (MES) in patients with Behçet's disease (BD). We also attempted to determine the frequency of MES in BD patients with or without neurological involvement. This study enrolled 55 patients fulfilling the diagnostic criteria of International Study Group for BD. Bilateral transcranial Doppler ultrasound of the middle cerebral arteries was performed. MES were identified based on the criteria of International Consensus group on Microembolus Detection. Patients with BD were divided into two groups in respect of the presence of neurological involvement (n = 10) or not (n = 45), and counts of MES in the two were compared with each other and with normal subjects. We found MES in 16 patients (29%) with BD. The frequency was higher in patients with neurological involvement than in those without (80% vs. 17%, P< 0.001). In patients with neurological involvement there was a positive correlation in regression analysis between the prevalence of MES and disease duration (P = 0.025). There was a significantly higher prevalence of MES in BD patients than in control subjects. The frequency of MES was higher in patients with neurological involvement than in those without. TCD detection of MES may allow the recognition of subset of patients at high risk for the appearance of neurological involvement.

Pulmonary involvement in juvenile systemic lupus erythematosus: a study on lung function in patients asymptomatic for respiratory disease.

Pleuro-pulmonary involvement has been well recognized in adults affected with systemic lupus erythematosus (SLE), but few studies have been carried out in children. A longitudinal study on a group of 15 children affected with juvenile SLE (JSLE), asymptomatic for lung disease, was performed, and the prevalence and the features of respiratory function alterations, over a period of 12 months, were analysed. Moreover, a possible correlation between any pulmonary function test (PFT) and disease duration, disease activity, visceral involvement and immunological pattern was evaluated. At baseline, a significant functional lung impairment was present in 40% of patients, with a significantly reduced FVC, VA and DLCO in 26% of them; in 60% of patients at 6 months and in 33% of patients at 12 months. At 6 and 12 months, our data did not show any significant modification in PFTs and the restrictive pattern, observed at baseline, remained unchanged. No correlation between altered PFTs and disease duration, activity and/or immunological findings was found. At baseline, the presence of neurological involvement was the only extra-pulmonary feature correlated to reduced FVC.

Predictors of prognosis and risk of acute renal failure in patients with Rocky Mountain spotted fever

Acute renal failure has long been associated with severe Rocky Mountain spotted fever (RMSF). Despite many descriptions of the protean manifestations of this disease, relatively little is known concerning the risk factors for acute renal failure. Only a few studies have examined the outcome of patients infected with Rickettsia rickettsii who develop renal insufficiency, and these studies had methodological problems. To study the incidence, risk factors, and outcomes of acute renal failure in a large group of hospitalized patients with definite or probable RMSF. The clinical records of 114 patients with definite or probable RMSF were retrospectively reviewed to identify clinical and biochemical abnormalities at the time of admission that were associated with the development of acute renal failure and subsequent mortality. Renal failure was defined as a serum creatinine (Cr) above 2 mg/dL. Logistic regression was used to study the association between these variables and the outcomes during hospitalization: death and the development of acute renal failure. The mortality rate in this series was 14%; 19% of the patients developed acute renal failure. The development of acute renal failure increased the odds ratio (OR) of dying by a factor of 17 (P = 0.001). Factors at the time of hospitalization that were associated at a univariate level with subsequent mortality included elevated serum Cr, increased age, increased level of AST, increased level of bilirubin, decreased serum sodium and platelet count, the presence of neurological involvement, and being male. Both the presence of neurological involvement and an elevated serum Cr at presentation were independently associated with increased mortality by multivariate analysis. Three patients developed acute renal failure that required hemodialysis, and only 1 of these 3 patients survived; he was ultimately discharged with a normal serum Cr. Factors at presentation that were associated with the development of acute renal failure included increased bilirubin, increasing age, thrombocytopenia, and the presence of neurological involvement. Both age and decreased platelet count at presentation were independently associated with the development of acute renal failure by multivariate analysis. Acute renal failure was a frequent complication of RMSF in this series of patients from a tertiary referral medical center. The presence of acute renal failure was strongly associated with death. Clinical and biochemical variables are useful in predicting which patients will develop acute renal failure.