Antecedent infections in Guillain-Barré syndrome in endemic areas of arbovirus transmission: A multinational case-control study.

Half of the world's population is at risk of arthropod-borne virus (arbovirus) infections. Several arbovirus infections have been associated with Guillain-Barré syndrome (GBS). We investigated whether arboviruses are driving GBS beyond epidemic phases of transmission and studied the antibody response to glycolipids. The protocol of the International Guillain-Barré syndrome Outcome Study (IGOS), an observational prospective cohort study, was adapted to a case-control design. Serum samples were tested for a recent infection with Zika virus (ZIKV), dengue virus (DENV), chikungunya (CHIKV) virus, hepatitis E virus, Epstein-Barr virus (EBV), cytomegalovirus (CMV), Campylobacter jejuni, and Mycoplasma pneumoniae, and for antibodies to glycolipids. Forty-nine patients were included from Brazil (63%), Argentina (14%), and Malaysia (22%). Evidence of a recent infection was found in 27/49 (55%) patients: C jejuni (n = 15, 31%), M pneumoniae (n = 5, 10%), CHIKV (n = 2, 4%), EBV (n = 1, 2%), C jejuni and M pneumoniae (n = 2, 4%), CMV and DENV (n = 1, 2%), and C jejuni and DENV (n = 1, 2%). In 22 patients, 35 paired controls were collected. Odds ratio for recent infections did not significantly differ between cases and controls. No typical anti-ganglioside antibody binding was associated with recent arbovirus infection. We conclude that arbovirus infections occur in GBS patients outside of epidemic viral transmission, although not significantly more than in controls. Broad infection and anti-ganglioside antibody serology are important to establish the most likely pathogenic trigger in GBS patients. Larger studies are necessary to determine the association between arboviruses and GBS.

Intraneural perineuriomas: diagnostic value of magnetic resonance neurography.

Intraneural perineurioma (IP) is an under-recognized hypertrophic peripheral nerve tumor. It affects young patients involving frequently the sciatic nerve and its branches and presents with a progressive, painless and predominantly motor deficit. Magnetic resonance neurography (MRN) is a useful tool to localize the lesion, evaluate its extension, and discriminate between different etiologies. We reviewed the clinical records of 11 patients with pathologically confirm IP. Eight patients were males with mean age 19 years. Initial complains were unilateral steppage (seven patients), bilateral steppage (one patient), unilateral gastrocnemius wasting (one patient), unilateral thigh atrophy (one patient), and unilateral hand weakness (one patient). Nine patients had mild painless sensory loss. Examinations revealed involvement of sciatic nerve extending into the peroneal nerve (eight patients), posterior tibial nerve (one patient), radial nerve (one patient), and femoral nerve (one patient). MRN revealed enlargement of the affected nerve isointense on T1-weighted, hyperintense on T2 fat-saturated images, and with avid enhancement on post-contrast imaging. In all patients, a nerve biopsy confirmed the diagnosis. MRN allows early and non-invasive identification of this tumor and is a key tool providing localization and differential diagnosis in patients with slowly progressive focal neuropathies.

Agalsidase alfa long-term effect on left ventricular hypertrophy in Fabry disease.

INTRODUCTION: Fabry disease (FD) is an X-linked lysosomal storage disorder affecting glycosphingolipid metabolism. Most FD patients have cardiac involvement, mainly manifested as left ventricular hypertrophy (LVH), leading to early death due to complications (arrhythmias, valvular disease, vascular involvement). Early initiation of enzyme replacement therapy (ERT) before fibrosis development has been associated with better cardiac outcomes in terms of left ventricular mass index (LVMI) and functional parameters. METHODS: A retrospective observational study was conducted in patients with FD treated with agalsidase alfa for at least 2 years. The primary objectives were: [a] to assess the annual rate of change in LVMI; [b] to define the overall incidence of stability, regression or progression of LVMI. RESULTS: Forty-nine patients were included in the final analysis, with a median follow-up of 7 years. The overall change in LVMI was 0.38 g/m2.73/year, without significant influence of baseline LVH, gender, age at ERT initiation, LV ejection fraction, body mass index, renal disease, and classical cardiovascular risk factors. Long-term ERT with agalsidase alfa was associated with stabilization of LVMI in 98% of patients with FD and was independent of the same covariables. CONCLUSION: Our results are in line with previous literature of comparable FD populations and probably represent the first study of its kind in Argentina. We here highlight the importance of cardiac morphometric stability as a positive outcome of ERT.

Introducción: La enfermedad de Fabry (EF) es una enfermedad de almacenamiento lisosomal ligada al cromosoma X que afecta el metabolismo de glicoesfingolípidos. La mayoría de pacientes EF tienen afectación cardíaca, manifestada principalmente como hipertrofia ventricular izquierda (HVI), que conduce a muerte prematura secundaria a complicaciones (arritmias, valvulopatías, afectación vascular). El tratamiento de reemplazo enzimático (TRE) precoz, iniciado antes del desarrollo de la fibrosis, se relaciona con mejores resultados cardíacos en términos del índice de masa ventricular izquierda (IMVI) y parámetros funcionales. Métodos: Se realizó un estudio retrospectivo observacional en que se incluyeron pacientes con EF tratados con agalsidasa alfa por al menos 2 años. Los objetivos primarios fueron: [a] evaluar el cambio anual del IMVI; [b] definir la incidencia global de estabilidad, regresión o progresión del IMVI. Resultados: Se incluyeron 49 pacientes, con seguimiento (mediana) de 7 años. El cambio global en el IMVI fue 0.38 g/m2.73/año, sin influencia significativa de HVI basal, sexo, edad de inicio de TRE, fracción de eyección del VI, índice de masa corporal, insuficiencia renal y factores de riesgo cardiovascular clásicos. La TRE a largo plazo con agalsidasa alfa se relacionó con la estabilización del IMVI en el 98% de los pacientes con EF, independientemente de las mismas covariables. Conclusión: Nuestros resultados están en línea con la bibliografía previa de poblaciones comparables y, probablemente, representan el primer estudio de este tipo en Argentina. Se destaca la importancia de la estabilidad morfométrica cardíaca como resultado positivo de la TRE.

[Chronic inflammatory sensory polyradiculopathy]. / Polirradiculopatía inflamatoria crónica sensitiva.

Chronic inflammatory sensory polyradiculopathy is a defined entity, frequently underdiagnosed, and potentially treatable. It must be suspected in patients with sensory ataxia, normal nerve conduction studies, and MRI with thickened lumbosacral nerve roots and gadolinium enhancement. We present the case of a 57-year-old man with marked sensory ataxia on his left leg. Examination showed normal strength, decreased knee and ankle jerks. Light touch and pinprick sensations were reduced below the knees. Vibration and joint position sense were absent at the feet. Nerve conduction studies were normal. Tibial sensory evoked potentials disclosed absent responses bilaterally. CSF was acellular with elevated protein. Lumbosacral magnetic resonance showed thickening of roots, with gadolinium enhancement. The patient was treated with IV-Ig, 2 g/kg, for 5 days with improvement of symptoms. The clinical course, elevated CSF protein, the evidence of root enhancement on the MRI, good response to immunotherapy, and the exclusion of other causes of sensory ataxia, were compatible with the diagnosis of chronic inflammatory sensory polyradiculopathy. To diagnose this disease the identification of isolated involvement of the sensory roots is required.

CSF Findings in Relation to Clinical Characteristics, Subtype, and Disease Course in Patients With Guillain-Barré Syndrome.

BACKGROUND AND OBJECTIVES: To investigate CSF findings in relation to clinical and electrodiagnostic subtypes, severity, and outcome of Guillain-Barré syndrome (GBS) based on 1,500 patients in the International GBS Outcome Study. METHODS: Albuminocytologic dissociation (ACD) was defined as an increased protein level (>0.45 g/L) in the absence of elevated white cell count (<50 cells/µL). We excluded 124 (8%) patients because of other diagnoses, protocol violation, or insufficient data. The CSF was examined in 1,231 patients (89%). RESULTS: In 846 (70%) patients, CSF examination showed ACD, which increased with time from weakness onset: ≤4 days 57%, >4 days 84%. High CSF protein levels were associated with a demyelinating subtype, proximal or global muscle weakness, and a reduced likelihood of being able to run at week 2 (odds ratio [OR] 0.42, 95% CI 0.25-0.70; p = 0.001) and week 4 (OR 0.44, 95% CI 0.27-0.72; p = 0.001). Patients with the Miller Fisher syndrome, distal predominant weakness, and normal or equivocal nerve conduction studies were more likely to have lower CSF protein levels. CSF cell count was <5 cells/µL in 1,005 patients (83%), 5-49 cells/µL in 200 patients (16%), and ≥50 cells/µL in 13 patients (1%). DISCUSSION: ACD is a common finding in GBS, but normal protein levels do not exclude this diagnosis. High CSF protein level is associated with an early severe disease course and a demyelinating subtype. Elevated CSF cell count, rarely ≥50 cells/µL, is compatible with GBS after a thorough exclusion of alternative diagnoses. CLASSIFICATION OF EVIDENCE: This study provides Class IV evidence that CSF ACD (defined by the Brighton Collaboration) is common in patients with GBS.

Predicting Outcome in Guillain-Barré Syndrome: International Validation of the Modified Erasmus GBS Outcome Score.

BACKGROUND AND OBJECTIVES: The clinical course and outcome of the Guillain-Barré syndrome (GBS) are diverse and vary among regions. The modified Erasmus GBS Outcome Score (mEGOS), developed with data from Dutch patients, is a clinical model that predicts the risk of walking inability in patients with GBS. The study objective was to validate the mEGOS in the International GBS Outcome Study (IGOS) cohort and to improve its performance and region specificity. METHODS: We used prospective data from the first 1,500 patients included in IGOS, aged ≥6 years and unable to walk independently. We evaluated whether the mEGOS at entry and week 1 could predict the inability to walk unaided at 4 and 26 weeks in the full cohort and in regional subgroups, using 2 measures for model performance: (1) discrimination: area under the receiver operating characteristic curve (AUC) and (2) calibration: observed vs predicted probability of being unable to walk independently. To improve the model predictions, we recalibrated the model containing the overall mEGOS score, without changing the individual predictive factors. Finally, we assessed the predictive ability of the individual factors. RESULTS: For validation of mEGOS at entry, 809 patients were eligible (Europe/North America [n = 677], Asia [n = 76], other [n = 56]), and 671 for validation of mEGOS at week 1 (Europe/North America [n = 563], Asia [n = 65], other [n = 43]). AUC values were >0.7 in all regional subgroups. In the Europe/North America subgroup, observed outcomes were worse than predicted; in Asia, observed outcomes were better than predicted. Recalibration improved model accuracy and enabled the development of a region-specific version for Europe/North America (mEGOS-Eu/NA). Similar to the original mEGOS, severe limb weakness and higher age were the predominant predictors of poor outcome in the IGOS cohort. DISCUSSION: mEGOS is a validated tool to predict the inability to walk unaided at 4 and 26 weeks in patients with GBS, also in countries outside the Netherlands. We developed a region-specific version of mEGOS for patients from Europe/North America. CLASSIFICATION OF EVIDENCE: This study provides Class II evidence that the mEGOS accurately predicts the inability to walk unaided at 4 and 26 weeks in patients with GBS. TRIAL REGISTRATION INFORMATION: NCT01582763.

Major cardiovascular adverse events in Fabry disease patients receiving agalsidase alfa.

Cardiovascular mortality (CVM) has become the major contributor to overall Fabry disease (FD) mortality in the enzyme replacement therapy (ERT) era. Our objectives were to describe causes and potential predictors of mortality in FD adult patients in Argentina, and to assess risk of major adverse cardiovascular events (MACE) in the ERT era. We retrospectively studied 93 consecutive patients treated with alphagalactosidase A (median follow up: 9.5 years from start of ERT). Mean age at ERT starting was 35 ± 16.3 years. Prevalence of cardiomyopathy and renal disease reached 47% and 41%, respectively. Eleven subjects (11.8%, 95% CI: 5-18%) died during follow up (1.24/100 patient-years). Mean overall survival was 71 years (95% CI: 66-75 years). Seven cases were considered as CVM; main causes were sudden death and stroke. Risk of MACE was 14% (95% CI: 6.9-21.1%; 1.47 events/100 patient-years from start of ERT). All but 2 subjects had at least one comorbid cardiovascular risk factor; however, 86% of patients remained free of MACE during follow-up. CVM remained low and our study was underpowered for detection of predictors of mortality, but it is worth noting that age at diagnosis and ERT starting, left ventricular mass index and renal disease trended to correlate with CVM. Prevalence of hypertension, diabetes and dyslipidemia were lower in FD patients when compared to population level data. As in the Argentinean general population, CVM was the leading cause of mortality among this cohort of consecutive FD patients treated with agalsidase alfa.

La mortalidad cardiovascular (MCV) se ha convertido en el principal contribuyente a la mortalidad general por enfermedad de Fabry (EF) en la era de la terapia de reemplazo enzimático (TRE). Nuestros objetivos fueron describir las causas y posibles predictores de mortalidad en pacientes adultos con EF en la Argentina, y evaluar el riesgo de eventos cardiovasculares mayores (MACE) en la actual era de TRE. Se estudiaron 93 pacientes consecutivos tratados con agalsidasa-alfa por una mediana de 9.5 años tras iniciar TRE. La edad al inicio de TRE fue 35 ± 16.3 años. La prevalencia de cardiomiopatía y enfermedad renal alcanzó 47% y 41%, respectivamente. Once sujetos (11.8%; IC95%: 5-18%) murieron durante el seguimiento (1.24/100 pacientes/año). La supervivencia global fue 71 años (IC95%: 66-75 años). Siete casos fueron considerados como MCV; las principales causas fueron muerte súbita e ictus. El riesgo de MACE fue 14% (IC95%: 6.9-21.1%; 1.47 eventos/100 pacientes/año desde la ERT). Todos menos 2 sujetos tenían al menos un factor de riesgo cardiovascular, pero el 86% permaneció libre de MACE. Los eventos de MCV fueron escasos. El estudio tuvo reducido poder estadístico para detectar predictores de mortalidad, pero la edad al diagnóstico y al iniciar la TRE, índice de masa ventricular izquierda y enfermedad renal tendieron a correlacionarse con MCV. La prevalencia de hipertensión, diabetes y dislipidemia fue menor en comparación con la población general. Como ocurre con la población general en Argentina, los eventos cardiovasculares fueron la principal causa de muerte en esta cohorte de pacientes consecutivos con EF tratados con agalsidasa-alfa.

Misdiagnosis in Fabry disease.

OBJECTIVE: To evaluate the most frequent diagnostic errors in patients with Fabry disease and the types of specialists most often consulted before diagnosis. STUDY DESIGN: We evaluated 45 consecutive symptomatic patients with Fabry disease confirmed by enzymatic tests in males and genetic studies in females. We interviewed the patients, their mothers, or both regarding symptoms, age at onset, medical consultations, and recommended treatments. RESULTS: Neuropathic pain was the most frequent initial complaint, and rheumatic fever was the most common diagnosis. Seven patients were treated with penicillin for many years. Ten patients sought medical consultation because of abdominal pain and were diagnosed with food intoxication or nonspecific pain. Six patients sought consultation because of anhidrosis, considered of unclear cause, and angiokeratomas diagnosed as petechiae. Internists and pediatricians were the most frequently consulted specialists. The correct diagnosis was obtained after a mean of 19.7 years. CONCLUSIONS: Pediatricians as well as internists commonly misdiagnose Fabry disease. Neuropathic pain, hypohidrosis, and recurrent abdominal pain in childhood or adolescence should include Fabry disease in the differential diagnosis to facilitate earlier diagnosis and treatment of these patients.

Agalsidase alfa long-term effect on left ventricular hypertrophy in Fabry disease / Efecto a largo plazo de la agalsidasa alfa sobre la hi pertrofia ventricular izquierda en la enfermedad de Fabry

Abstract Introduction : Fabry disease (FD) is an X-linked ly sosomal storage disorder affecting glycosphingolipid metabolism. Most FD patients have cardiac involvement, mainly manifested as left ventricular hypertrophy (LVH), leading to early death due to complications (arrhyth mias, valvular disease, vascular involvement). Early initiation of enzyme replacement therapy (ERT) before fibrosis development has been associated with better cardiac outcomes in terms of left ventricular mass index (LVMI) and functional parameters. Methods : A retrospective observational study was conducted in patients with FD treated with agalsidase alfa for at least 2 years. The primary objectives were: [a] to assess the annual rate of change in LVMI; [b] to define the overall incidence of stability, regression or progression of LVMI. Results : Forty-nine patients were included in the final analysis, with a median follow-up of 7 years. The overall change in LVMI was 0.38 g/m2.73/year, without significant influence of baseline LVH, gender, age at ERT initiation, LV ejection fraction, body mass index, renal disease, and classical cardiovascular risk factors. Long-term ERT with agalsidase alfa was associated with stabilization of LVMI in 98% of patients with FD and was independent of the same covariables. Conclusion : Our results are in line with previous literature of comparable FD populations and probably represent the first study of its kind in Argentina. We here highlight the importance of cardiac morphomet ric stability as a positive outcome of ERT.

Resumen Introducción : La enfermedad de Fabry (EF) es una enfermedad de almacenamiento lisosomal ligada al cromosoma X que afecta el metabolismo de glicoes fingolípidos. La mayoría de pacientes EF tienen afec tación cardíaca, manifestada principalmente como hipertrofia ventricular izquierda (HVI), que conduce a muerte prematura secundaria a complicaciones (arritmias, valvulopatías, afectación vascular). El trata miento de reemplazo enzimático (TRE) precoz, iniciado antes del desarrollo de la fibrosis, se relaciona con mejores resultados cardíacos en términos del índice de masa ventricular izquierda (IMVI) y parámetros funcionales. Métodos : Se realizó un estudio retrospectivo obser vacional en que se incluyeron pacientes con EF tratados con agalsidasa alfa por al menos 2 años. Los objetivos primarios fueron: [a] evaluar el cambio anual del IMVI; [b] definir la incidencia global de estabilidad, regresión o progresión del IMVI. Resultados : Se incluyeron 49 pacientes, con segui miento (mediana) de 7 años. El cambio global en el IMVI fue 0.38 g/m2.73/año, sin influencia significativa de HVI basal, sexo, edad de inicio de TRE, fracción de eyección del VI, índice de masa corporal, insuficiencia renal y factores de riesgo cardiovascular clásicos. La TRE a largo plazo con agalsidasa alfa se relacionó con la estabilización del IMVI en el 98% de los pacientes con EF, independientemente de las mismas covariables. Conclusión : Nuestros resultados están en línea con la bibliografía previa de poblaciones comparables y, pro bablemente, representan el primer estudio de este tipo en Argentina. Se destaca la importancia de la estabilidad morfométrica cardíaca como resultado positivo de la TRE.

Neuro-Otological and Peripheral Nerve Involvement in Fabry Disease.

Fabry disease (FD) is an X-linked lysosomal storage disease, with multisystemic glycosphingolipids deposits. Neuro-otological involvement leading to hearing loss and vestibular dysfunctions has been described, but there is limited information about the frequency, site of lesion, or the relationship with peripheral neuropathy. The aim was to evaluate the presence of auditory and vestibular symptoms, and assess neurophysiological involvement of the VIII cranial nerve, correlating these findings with clinical and neurophysiological features of peripheral neuropathy. We studied 36 patients with FD with a complete neurological and neuro-otological evaluation including nerve conduction studies, quantitative sensory testing (to evaluate small fiber by warm and cold threshold detection and cold and heat pain), vestibular evoked myogenic potentials, videonistagmography, audiometry and brainstem auditory evoked potentials. Neuro-otologic symptoms included hearing loss (22.2%), vertigo (27.8%) or both (25%). An involvement of either cochlear or vestibular function was identified in most patients (75%). In 70% of our patients the involvement of both cochlear and vestibular function could not be explained by a neural or vascular mechanism. Small fiber neuropathy was identified in 77.7%. There were no significant associations between neuro-otological and QST abnormalities. Neuro-otologic involvement is frequent and most likely under-recognized in patients with FD. It lacks a specific neural or vascular pattern, suggesting multi-systemic, end organ damage. Small fiber neuropathy is an earlier manifestation of FD, but there is no correlation between the development of neuropathy and neuro-otological abnormalities.

Depression: The Hidden Problem in Fabry Disease. A Review

Abstract Fabry disease (FD) is an X-linked disorder of glycosphingolipids caused by mutations of the GLA gene. The classical form presents with neuropathic pain and gastrointestinal complaints since childhood or adolescence and progressing into adulthood with ischemic stroke, cardiac dysfunction, and chronic kidney disease. Depression seems to be a frequent complication of FD but its frequently underdiagnosed and undertreated. Comorbid depression in different chronic diseases has been associated with an overall increase in disease burden and medical costs, impairment in activities of daily living, and impact on self-care and treatment adherence. In addition, a clear association between pain and depression has been observed in FD patients and appears to have an unequivocal neurobiological matrix. The aim of this review is to provide an overview of the literature on depression in patients with FD and to highlight some of the emerging issues on this topic. Further research to improve detection and to develop effective treatments for depression in this population is promptly needed.

Major cardiovascular adverse events in Fabry disease patients receiving agalsidase alfa / Eventos cardiovasculares mayores en pacientes con enfermedad de Fabry tratados con agalsidasa alfa

Abstract Cardiovascular mortality (CVM) has become the major contributor to overall Fabry disease (FD) mortality in the enzyme replacement therapy (ERT) era. Our objectives were to describe causes and potential predictors of mortality in FD adult patients in Argentina, and to assess risk of major adverse cardio vascular events (MACE) in the ERT era. We retrospectively studied 93 consecutive patients treated with alpha-galactosidase A (median follow up: 9.5 years from start of ERT). Mean age at ERT starting was 35±16.3 years. Prevalence of cardiomyopathy and renal disease reached 47% and 41%, respectively. Eleven subjects (11.8%, 95%CI: 5-18%) died during follow up (1.24/100 patient-years). Mean overall survival was 71 years (95%CI: 66-75 years). Seven cases were considered as CVM; main causes were sudden death and stroke. Risk of MACE was 14% (95%CI: 6.9-21.1%; 1.47 events/100 patient-years from start of ERT). All but 2 subjects had at least one comorbid cardiovascular risk factor; however, 86% of patients remained free of MACE during follow-up. CVM remained low and our study was underpowered for detection of predictors of mortality, but it is worth noting that age at diagnosis and ERT starting, left ventricular mass index and renal disease trended to correlate with CVM. Prevalence of hypertension, diabetes and dyslipidemia were lower in FD patients when compared to population level data. As in the Argentinean general population, CVM was the leading cause of mortality among this cohort of consecutive FD patients treated with agalsidase alfa.

Resumen La mortalidad cardiovascular (MCV) se ha convertido en el principal contribuyente a la mortalidad general por enfermedad de Fabry (EF) en la era de la terapia de reemplazo enzimático (TRE). Nuestros objetivos fueron describir las causas y posibles predictores de mortalidad en pacientes adultos con EF en la Argentina, y evaluar el riesgo de eventos cardiovasculares mayores (MACE) en la actual era de TRE. Se estudiaron 93 pacientes consecutivos tratados con agalsidasa-alfa por una mediana de 9.5 años tras iniciar TRE. La edad al inicio de TRE fue 35 ± 16.3 años. La prevalencia de cardiomiopatía y enfermedad renal alcanzó 47% y 41%, respectivamente. Once sujetos (11.8%; IC95%: 5-18%) murieron durante el seguimiento (1.24/100 pacientes/año). La supervivencia global fue 71 años (IC95%: 66-75 años). Siete casos fueron considerados como MCV; las principales causas fueron muerte súbita e ictus. El riesgo de MACE fue 14% (IC95%: 6.9-21.1%; 1.47 eventos/100 pacientes/año desde la ERT). Todos menos 2 sujetos tenían al menos un factor de riesgo cardiovascular, pero el 86% permaneció libre de MACE. Los eventos de MCV fueron escasos. El estudio tuvo reducido poder estadístico para detectar predictores de mortalidad, pero la edad al diagnóstico y al iniciar la TRE, índice de masa ventricular izquierda y enfermedad renal tendieron a correlacionarse con MCV. La prevalencia de hipertensión, diabetes y dislipidemia fue menor en comparación con la población general. Como ocurre con la población general en Argentina, los eventos cardiovasculares fueron la principal causa de muerte en esta cohorte de pacientes consecutivos con EF tratados con agalsidasa-alfa.

Multifocal motor neuropathy, type 1 diabetes and asymptomatic Hashimoto's thyroiditis: an unusual association.

Immune mediated mechanisms play a role in some forms of diabetic neuropathies. We studied a 17-year-old man who developed asymmetric weakness and atrophy in both upper arms soon after the diagnosis of type 1 diabetes. Nerve conduction studies demonstrated multifocal motor conduction blocks, and serological investigations revealed subclinical Hashimoto's thyroiditis. Therapy with intravenous immunoglobulin and cyclophosphamide led to clinical recovery. This is the first observation of an association between type 1 diabetes, multifocal motor neuropathy and Hashimoto's thyroiditis.

Brain MRI findings in patients with Fabry disease.

BACKGROUND: To evaluate the presence of ischemic and hemorrhagic lesions in brain MRI of patients with Fabry disease (FD). METHODS: Brain MRI studies in 46 consecutive patients were evaluated using classic sequences as well as GRE-weighted images, for ischemic lesions and chronic microbleed detection. Of the 36 adult patients (15 males, mean age 31.2 years; 21 females, mean age 41.6 years). All had signs or symptoms of FD but lacked history of stroke or TIA. RESULTS: Ten patients under 20 years of age initially presented a normal MRI. One child developed a hyperintense occipital lesion on T2-weighted imaging during control MRI. Sixteen adult patients (44.4%) had brain MRI evidence of small vessel disease in the basal ganglia, corona radiata, thalamus or brainstem, as well as in the periventricular white matter. Patients with MRI abnormalities were older (45.6 vs 30.9 years, p=0.005), with more vascular risk factors (1.2 vs 0.6 p=0.043). Three women (mean age 59.5 years) presented deep chronic microbleeds identified by GRE. Moreover, Flair and T2-weighted images revealed white matter disease and deep gray matter involvement. CONCLUSION: 44.4% of adult patients with FD without clinical history of CVA or prior dialysis had evidence of small vessel disease on MRI and 11% showed cerebral microbleeds. FD is a treatable disorder that should be routinely included in the differential diagnosis of ischemic and microhemorrhagic lesions in young adults.

Polirradiculopatía inflamatoria crónica sensitiva / Chronic inflammatory sensory polyradiculopathy

La polirradiculopatía inflamatoria crónica sensitiva es una entidad definida, frecuentemente subdiagnosticada y potencialmente tratable. Debe ser sospechada en pacientes con ataxia sensitiva, estudios de conducción nerviosa normales y una resonancia magnética que muestre engrosamiento y realce con gadolinio de las raíces lumbosacras. Presentamos el caso de un hombre de 57 años de edad con marcada ataxia sensitiva en pierna izquierda. Al examen físico presentaba fuerza conservada, reflejos osteotendinosos disminuidos, tacto fino y superficial reducidos por debajo de las rodillas; abatiestesia y apalestesia en ambos pies. Los estudios de conducción nerviosa eran normales, los potenciales evocados somatosensitivos tibiales con ausencia de respuesta bilateral. El líquido cefalorraquídeo presentaba hiperproteinorraquia sin células. La resonancia magnética mostró engrosamiento y realce con gadolinio de las raíces lumbosacras. El paciente fue tratado con inmunoglobulina endovenosa (IgEV) a 2 g/kg durante 5 días, con buena respuesta. La evolución clínica, la hiperproteinorraquia, el realce de raíces en la resonancia magnética, la buena respuesta a la inmunoterapia y la exclusión de otras causas de ataxia sensitiva fueron compatibles con el diagnóstico de polirradiculopatía inflamatoria crónica sensitiva. Para el diagnóstico de esta enfermedad se requiere la identificación del compromiso aislado de las raíces sensitivas.

Chronic inflammatory sensory polyradiculopathy is a defined entity, frequently underdiagnosed, and potentially treatable. It must be suspected in patients with sensory ataxia, normal nerve conduction studies, and MRI with thickened lumbosacral nerve roots and gadolinium enhancement. We present the case of a 57-year-old man with marked sensory ataxia on his left leg. Examination showed normal strength, decreased knee and ankle jerks. Light touch and pinprick sensations were reduced below the knees. Vibration and joint position sense were absent at the feet. Nerve conduction studies were normal. Tibial sensory evoked potentials disclosed absent responses bilaterally. CSF was acellular with elevated protein. Lumbosacral magnetic resonance showed thickening of roots, with gadolinium enhancement. The patient was treated with IV-Ig, 2 g/kg, for 5 days with improvement of symptoms. The clinical course, elevated CSF protein, the evidence of root enhancement on the MRI, good response to immunotherapy, and the exclusion of other causes of sensory ataxia, were compatible with the diagnosis of chronic inflammatory sensory polyradiculopathy. To diagnose this disease the identification of isolated involvement of the sensory roots is required.