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Fabry disease - underestimated in the differential diagnosis of multiple sclerosis?

Böttcher T, Rolfs A, Tanislav C, Bitsch A, Köhler W, Gaedeke J, Giese AK, Kolodny EH, Duning T - PLoS ONE (2013)

Bottom Line: The lesion pattern and results of cerebrospinal fluid examination were inconsistent and non-specific.White matter lesion volumes ranged from 8.9 mL to 34.8 mL (mean 17.8 mL±11.4 mL).There was no association between extra-neurological manifestations or enzyme activity and lesion load.

View Article: PubMed Central - PubMed

Affiliation: Albrecht Kossel Institute for Neuroregeneration, University of Rostock, Rostock, Germany ; Department of Neurology, Dietrich-Bonhoeffer-Klinikum, Neubrandenburg, Germany.

ABSTRACT

Objective: Fabry disease is a rare X-linked inherited lysosomal storage disorder affecting multiple organ systems. It includes central nervous system involvement via micro- and macroangiopathic cerebral changes. Due to its clinical symptoms and frequent MRI lesions, Fabry disease is commonly misdiagnosed as multiple sclerosis. We present an overview of cases from Fabry centres in Germany initially misdiagnosed with multiple sclerosis and report the clinical, MR-tomographical, and laboratory findings.

Methods: Eleven Fabry patients (one male, ten females) initially diagnosed with multiple sclerosis were identified from 187 patient records (5.9%) and analyzed for presenting symptoms, results of the initial diagnostic workup, and the clinical course of the disease.

Results: Four patients were identified as having a "possible" history of MS, and 7 patients as "definite" cases of multiple sclerosis (revised McDonald criteria). On average, Fabry disease was diagnosed 8.2 years (±9.8 years) after the MS diagnosis, and 12.8 years after onset of first symptoms (±10.3 years). All patients revealed white matter lesions on MRI. The lesion pattern and results of cerebrospinal fluid examination were inconsistent and non-specific. White matter lesion volumes ranged from 8.9 mL to 34.8 mL (mean 17.8 mL±11.4 mL). There was no association between extra-neurological manifestations or enzyme activity and lesion load.

Conclusion: There are several anamnestic and clinical hints indicating when Fabry disease should be considered a relevant differential diagnosis of multiple sclerosis, e.g. female patients with asymmetric, confluent white matter lesions on MRI, normal spinal MR imaging, ectatic vertebrobasilar arteries, proteinuria, or lack of intrathecally derived immunoglobulin synthesis.

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MR images (T2-weighted and FLAIR sequences) of 11 Fabry patients misdiagnosed with multiple sclerosis.Upper row: Patients 7, 5, 8 and 9 showed more punctuate and subcortical white matter lesions (yellow circles). Second row: White matter lesions in patients 1, 4, and 3 had a rather confluent, periventricular pattern (red circles). This pattern was associated with “black holes” (white circles) in T1-weighted images as a surrogate of severe demyelination and axonal injury. Third row: Patients 2, 10, and 11 revealed both disseminated and confluent, periventricular patterns. Fourth row: Only patient 6 showed an uncommon image with a severe, asymmetrical involvement of cortical, subcortical, and basal ganglia tissues.
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pone-0071894-g001: MR images (T2-weighted and FLAIR sequences) of 11 Fabry patients misdiagnosed with multiple sclerosis.Upper row: Patients 7, 5, 8 and 9 showed more punctuate and subcortical white matter lesions (yellow circles). Second row: White matter lesions in patients 1, 4, and 3 had a rather confluent, periventricular pattern (red circles). This pattern was associated with “black holes” (white circles) in T1-weighted images as a surrogate of severe demyelination and axonal injury. Third row: Patients 2, 10, and 11 revealed both disseminated and confluent, periventricular patterns. Fourth row: Only patient 6 showed an uncommon image with a severe, asymmetrical involvement of cortical, subcortical, and basal ganglia tissues.

Mentions: MRI scans of all patients revealed cerebral white matter lesions. Localization of the WML was primarily subcortical, with punctuate lesions in 4 cases. 3 patients showed mainly periventricular confluent WML. Three other patients had both periventricular and subcortical WML localizations. For one patient (no. 6), an uncommon MR image documenting a severe asymmetrical involvement of the cortical, subcortical, and basal ganglia tissues was derived (Figure 1). Gadolinium enhancement was not observed in any of the cases. MRI scans of the spinal cord were unrevealing in all cases.


Fabry disease - underestimated in the differential diagnosis of multiple sclerosis?

Böttcher T, Rolfs A, Tanislav C, Bitsch A, Köhler W, Gaedeke J, Giese AK, Kolodny EH, Duning T - PLoS ONE (2013)

MR images (T2-weighted and FLAIR sequences) of 11 Fabry patients misdiagnosed with multiple sclerosis.Upper row: Patients 7, 5, 8 and 9 showed more punctuate and subcortical white matter lesions (yellow circles). Second row: White matter lesions in patients 1, 4, and 3 had a rather confluent, periventricular pattern (red circles). This pattern was associated with “black holes” (white circles) in T1-weighted images as a surrogate of severe demyelination and axonal injury. Third row: Patients 2, 10, and 11 revealed both disseminated and confluent, periventricular patterns. Fourth row: Only patient 6 showed an uncommon image with a severe, asymmetrical involvement of cortical, subcortical, and basal ganglia tissues.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3756019&req=5

pone-0071894-g001: MR images (T2-weighted and FLAIR sequences) of 11 Fabry patients misdiagnosed with multiple sclerosis.Upper row: Patients 7, 5, 8 and 9 showed more punctuate and subcortical white matter lesions (yellow circles). Second row: White matter lesions in patients 1, 4, and 3 had a rather confluent, periventricular pattern (red circles). This pattern was associated with “black holes” (white circles) in T1-weighted images as a surrogate of severe demyelination and axonal injury. Third row: Patients 2, 10, and 11 revealed both disseminated and confluent, periventricular patterns. Fourth row: Only patient 6 showed an uncommon image with a severe, asymmetrical involvement of cortical, subcortical, and basal ganglia tissues.
Mentions: MRI scans of all patients revealed cerebral white matter lesions. Localization of the WML was primarily subcortical, with punctuate lesions in 4 cases. 3 patients showed mainly periventricular confluent WML. Three other patients had both periventricular and subcortical WML localizations. For one patient (no. 6), an uncommon MR image documenting a severe asymmetrical involvement of the cortical, subcortical, and basal ganglia tissues was derived (Figure 1). Gadolinium enhancement was not observed in any of the cases. MRI scans of the spinal cord were unrevealing in all cases.

Bottom Line: The lesion pattern and results of cerebrospinal fluid examination were inconsistent and non-specific.White matter lesion volumes ranged from 8.9 mL to 34.8 mL (mean 17.8 mL±11.4 mL).There was no association between extra-neurological manifestations or enzyme activity and lesion load.

View Article: PubMed Central - PubMed

Affiliation: Albrecht Kossel Institute for Neuroregeneration, University of Rostock, Rostock, Germany ; Department of Neurology, Dietrich-Bonhoeffer-Klinikum, Neubrandenburg, Germany.

ABSTRACT

Objective: Fabry disease is a rare X-linked inherited lysosomal storage disorder affecting multiple organ systems. It includes central nervous system involvement via micro- and macroangiopathic cerebral changes. Due to its clinical symptoms and frequent MRI lesions, Fabry disease is commonly misdiagnosed as multiple sclerosis. We present an overview of cases from Fabry centres in Germany initially misdiagnosed with multiple sclerosis and report the clinical, MR-tomographical, and laboratory findings.

Methods: Eleven Fabry patients (one male, ten females) initially diagnosed with multiple sclerosis were identified from 187 patient records (5.9%) and analyzed for presenting symptoms, results of the initial diagnostic workup, and the clinical course of the disease.

Results: Four patients were identified as having a "possible" history of MS, and 7 patients as "definite" cases of multiple sclerosis (revised McDonald criteria). On average, Fabry disease was diagnosed 8.2 years (±9.8 years) after the MS diagnosis, and 12.8 years after onset of first symptoms (±10.3 years). All patients revealed white matter lesions on MRI. The lesion pattern and results of cerebrospinal fluid examination were inconsistent and non-specific. White matter lesion volumes ranged from 8.9 mL to 34.8 mL (mean 17.8 mL±11.4 mL). There was no association between extra-neurological manifestations or enzyme activity and lesion load.

Conclusion: There are several anamnestic and clinical hints indicating when Fabry disease should be considered a relevant differential diagnosis of multiple sclerosis, e.g. female patients with asymmetric, confluent white matter lesions on MRI, normal spinal MR imaging, ectatic vertebrobasilar arteries, proteinuria, or lack of intrathecally derived immunoglobulin synthesis.

Show MeSH
Related in: MedlinePlus