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Neurological manifestations of Ehlers-Danlos syndrome(s): A review.

Castori M, Voermans NC - Iran J Neurol (2014)

Bottom Line: The emerging picture defines a wide spectrum of neurological manifestations that are unexpectedly common and potentially disabling.Their evaluation and correct interpretation by the clinical neurologist is crucial for avoiding superfluous investigations, wrong therapies, and inappropriate referral.A set of basic tools for patient's recognition is offered for raising awareness among neurologists on this underdiagnosed group of hereditary disorders.

View Article: PubMed Central - PubMed

Affiliation: Department of Medical Genetics, San Camillo-Forlanini Hospital, Sapienza University of Rome and San Camillo - Forlanin, Rome, Italy.

ABSTRACT
The term "Ehlers-Danlos syndrome" (EDS) groups together an increasing number of heritable connective tissue disorders mainly featuring joint hypermobility and related complications, dermal dysplasia with abnormal skin texture and repair, and variable range of the hollow organ and vascular dysfunctions. Although the nervous system is not considered a primary target of the underlying molecular defect, recently, increasing attention has been posed on neurological manifestations of EDSs, such as musculoskeletal pain, fatigue, headache, muscle weakness and paresthesias. Here, a comprehensive overview of neurological findings of these conditions is presented primarily intended for the clinical neurologist. Features are organized under various subheadings, including pain, fatigue, headache, stroke and cerebrovascular disease, brain and spine structural anomalies, epilepsy, muscular findings, neuropathy and developmental features. The emerging picture defines a wide spectrum of neurological manifestations that are unexpectedly common and potentially disabling. Their evaluation and correct interpretation by the clinical neurologist is crucial for avoiding superfluous investigations, wrong therapies, and inappropriate referral. A set of basic tools for patient's recognition is offered for raising awareness among neurologists on this underdiagnosed group of hereditary disorders.

No MeSH data available.


Related in: MedlinePlus

Periventricular heterotopias in a 37-year-old woman with features of classic Ehlers-Danlos syndrome
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Figure 2: Periventricular heterotopias in a 37-year-old woman with features of classic Ehlers-Danlos syndrome

Mentions: Brain magnetic resonance imaging (MRI) is usually unremarkable for major structural anomalies in EDS. Therefore, with the exception of acute presentations with the suspect of cerebrovascular disease, such an investigation usually does not take place in the baseline assessment of EDS patients. Nevertheless, the presence of clear-cut X-linked dominant transmission and/or the coexistence of seizures should elicit the exclusion of the rare form of EDS with periventricular heterotopias (Figure 2) often due to mutations in FLNA.76,77 Single reports also associate EDS with polymycrogyria,78 agenesis of the corpus callosum,79 dilatation of the 4th ventricle, supracerebellar cistern and lateral ventricle, or disproportional enlargement of anterior horn of lateral ventricle,80 but the consistency of such associations awaits confirmation. Conversely, clinical practice suggests a high rate of degenerative findings, in the form of generalized, early-onset spondylosis and disc hernias, at spine MRI. However, this evidence remains anecdotal81 and needs systematic confirmation. Spine MRI may also show meningeal cysts as reported in a 7-year-old girl with kyphoscoliotic EDS,82 in an adult with classic EDS83 and, with a low frequency, in JHS/EDS-HT.84 In EDS, meningeal (or Tarlov) cysts are apparently rare and very few or single. The 40-year-old woman with multiple and bilateral Tarlov cysts along the entire spine and originally defined an example of (unclassified) EDS by Isono et al.,85 can be best labeled with the diagnosis of lateral meningocele syndrome,86 an apparently distinct form of hereditary connective tissue disorder with severe thecal involvement.87 The clinical significance of meningeal cysts is still unknown in EDS, although a link with orthostatic headache due to spontaneous cerebrospinal fluid leaks may be inferred,88,89 similarly as in Marfan syndrome. The concurrence of Chiari malformation (Type I) is a further apparently underreported feature of EDS, as to date observed in single patients only.45,46 Nevertheless, in a surgically-oriented paper on hundreds of patients originally ascertained for symptomatic Chiari malformation, a subgroup of them, showing a high rate of recurrence after surgery and multiple features of an underlying connective tissue disorder, presented minor, but measurable neuroradiologic features of occipitoatlantoaxial instability: posterior gliding of the occipital condyles, and reduction of the clivus-axis angle, clivus-atlas angle, and atlas-axis angle in the upright position.90 In line with this, an early report describes two vascular EDS patients with radiologically evident atlantoaxial subluxation.91 Hence, investigating for cerebellar tonsils herniation and an occult occipitoatlantoaxial instability is relevant during the assessment of patients with occipital or postural/orthostatic headache, and/or additional unexplained neurological symptoms, such as upper limb paresthesias and weakness.


Neurological manifestations of Ehlers-Danlos syndrome(s): A review.

Castori M, Voermans NC - Iran J Neurol (2014)

Periventricular heterotopias in a 37-year-old woman with features of classic Ehlers-Danlos syndrome
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4300794&req=5

Figure 2: Periventricular heterotopias in a 37-year-old woman with features of classic Ehlers-Danlos syndrome
Mentions: Brain magnetic resonance imaging (MRI) is usually unremarkable for major structural anomalies in EDS. Therefore, with the exception of acute presentations with the suspect of cerebrovascular disease, such an investigation usually does not take place in the baseline assessment of EDS patients. Nevertheless, the presence of clear-cut X-linked dominant transmission and/or the coexistence of seizures should elicit the exclusion of the rare form of EDS with periventricular heterotopias (Figure 2) often due to mutations in FLNA.76,77 Single reports also associate EDS with polymycrogyria,78 agenesis of the corpus callosum,79 dilatation of the 4th ventricle, supracerebellar cistern and lateral ventricle, or disproportional enlargement of anterior horn of lateral ventricle,80 but the consistency of such associations awaits confirmation. Conversely, clinical practice suggests a high rate of degenerative findings, in the form of generalized, early-onset spondylosis and disc hernias, at spine MRI. However, this evidence remains anecdotal81 and needs systematic confirmation. Spine MRI may also show meningeal cysts as reported in a 7-year-old girl with kyphoscoliotic EDS,82 in an adult with classic EDS83 and, with a low frequency, in JHS/EDS-HT.84 In EDS, meningeal (or Tarlov) cysts are apparently rare and very few or single. The 40-year-old woman with multiple and bilateral Tarlov cysts along the entire spine and originally defined an example of (unclassified) EDS by Isono et al.,85 can be best labeled with the diagnosis of lateral meningocele syndrome,86 an apparently distinct form of hereditary connective tissue disorder with severe thecal involvement.87 The clinical significance of meningeal cysts is still unknown in EDS, although a link with orthostatic headache due to spontaneous cerebrospinal fluid leaks may be inferred,88,89 similarly as in Marfan syndrome. The concurrence of Chiari malformation (Type I) is a further apparently underreported feature of EDS, as to date observed in single patients only.45,46 Nevertheless, in a surgically-oriented paper on hundreds of patients originally ascertained for symptomatic Chiari malformation, a subgroup of them, showing a high rate of recurrence after surgery and multiple features of an underlying connective tissue disorder, presented minor, but measurable neuroradiologic features of occipitoatlantoaxial instability: posterior gliding of the occipital condyles, and reduction of the clivus-axis angle, clivus-atlas angle, and atlas-axis angle in the upright position.90 In line with this, an early report describes two vascular EDS patients with radiologically evident atlantoaxial subluxation.91 Hence, investigating for cerebellar tonsils herniation and an occult occipitoatlantoaxial instability is relevant during the assessment of patients with occipital or postural/orthostatic headache, and/or additional unexplained neurological symptoms, such as upper limb paresthesias and weakness.

Bottom Line: The emerging picture defines a wide spectrum of neurological manifestations that are unexpectedly common and potentially disabling.Their evaluation and correct interpretation by the clinical neurologist is crucial for avoiding superfluous investigations, wrong therapies, and inappropriate referral.A set of basic tools for patient's recognition is offered for raising awareness among neurologists on this underdiagnosed group of hereditary disorders.

View Article: PubMed Central - PubMed

Affiliation: Department of Medical Genetics, San Camillo-Forlanini Hospital, Sapienza University of Rome and San Camillo - Forlanin, Rome, Italy.

ABSTRACT
The term "Ehlers-Danlos syndrome" (EDS) groups together an increasing number of heritable connective tissue disorders mainly featuring joint hypermobility and related complications, dermal dysplasia with abnormal skin texture and repair, and variable range of the hollow organ and vascular dysfunctions. Although the nervous system is not considered a primary target of the underlying molecular defect, recently, increasing attention has been posed on neurological manifestations of EDSs, such as musculoskeletal pain, fatigue, headache, muscle weakness and paresthesias. Here, a comprehensive overview of neurological findings of these conditions is presented primarily intended for the clinical neurologist. Features are organized under various subheadings, including pain, fatigue, headache, stroke and cerebrovascular disease, brain and spine structural anomalies, epilepsy, muscular findings, neuropathy and developmental features. The emerging picture defines a wide spectrum of neurological manifestations that are unexpectedly common and potentially disabling. Their evaluation and correct interpretation by the clinical neurologist is crucial for avoiding superfluous investigations, wrong therapies, and inappropriate referral. A set of basic tools for patient's recognition is offered for raising awareness among neurologists on this underdiagnosed group of hereditary disorders.

No MeSH data available.


Related in: MedlinePlus