Characterizing a new clinical phenotype: the co-existence of cerebral venous outflow and connective tissue disorders

Abstract

BackgroundThere is increasing recognition of connective tissue disorders and their influence on disease in the general population. A conserved clinical phenotype involving connective tissue disorders and idiopathic intracranial hypertension (IIH) and associated cerebral venous outflow disorders (CVD) has not been previously described.MethodsA single-institution retrospective review of a prospectively maintained database of patients with connective tissue disorders and CVD was performed.ResultsA total of 86 patients were identified. The majority of these patients carried a diagnosis of Ehlers-Danlos syndrome (55%) and most were non-obese (mean body mass index 29.7 kg/m2), Caucasian (90%) females (87%). Most prevalent presenting symptoms included pressure headache (98%), dizziness (90%), tinnitus (92%), and cognitive dysfunction (69%). Aside from CVD and IIH, the most common associated conditions were postural orthostatic tachycardia syndrome (POTS; 55.8%), cerebrospinal fluid (CSF) leaks (51.2%), dysautonomia (45.3%), cranio-cervical instability (37.2%), mast cell activation syndrome (25.6%), and tethered cord syndrome (23.3%). Allergies to medications (87.2%) and surgical tape (19.8%) were also frequent. Despite significantly lower opening pressures on lumbar puncture, headache severity and quality of life scores were reported with the same severity of classic IIH patients, suggesting an underlying hypersensitivity to intracranial pressures and cerebral venous congestion.ConclusionThere is a rare but conserved clinical phenotype that has not been described previously that presents with severe IIH symptoms in predominantly young, non-obese Caucasian women with a high associated incidence of dysautonomia, POTS, craniocervical instability, and CSF leaks, among others.

Hypermobile Ehlers-Danlos syndrome and spontaneous CSF leaks: the connective tissue conundrum

“…Recognizing transverse sinus stenosis as a key factor in intracranial venous hypertension has increased the use of catheter venography to evaluate stenting candidates and advance research into cerebral venous anatomy and disease mechanisms, deepening the understanding of cerebral venous outflow disorders (CVD) within the IIH spectrum. In a retrospective study of 86 patients with diagnosed or suspected CTDs being evaluated for cerebral venous outflow disorders (CVD), the following prevalence of conditions was observed IIH (75.6%), CSF leaks (51.2%), dysautonomia (45.3%), EDS (55.8%), MCAD (25.6%) and systemic venous compression syndrome in (10.5%) ( 24 ). This study describes significant differences in patient profile from the typical demographic of obese women of childbearing age from diverse racial backgrounds.…”

“…The demographic observed in suspected or diagnosed CTDs with IIH have a lower mean BMI and consist mainly of non-obese Caucasian young women. This population presents with more severe symptoms at lower lumbar puncture opening pressures, lower mean superior sagittal sinus pressures on venography compared to standard IIH patients, and report an increased severity of headaches and worse quality of life ( 24 ). This suggests a hypersensitivity to pain and/or pressure dysregulation associated with CTDs and highlights the necessity for a better understanding of cerebral venous disorders and connective tissue conditions, as symptoms in these patients may present with increased severity and persist at lower intracranial pressures than typically expected.…”

“…In a retrospective study of 86 patients with diagnosed CTDs and cerebral venous outflow disorders including idiopathic intracranial hypertension (IIH), significant comorbidities were identified including POTS (55.8%), dysautonomia (45.3%), CCI (37.2%), MCAD (25.6%), and TCS (23.3%), while a second study of 2,149 patients with hEDS found 70.87% has dysautonomia/POTS, 31.60% had CCI/AAI, 7.91% had CM, and 6.75% had TCS ( 24 , 34 ). Some cases of CSF leaks may be linked to TCS or tethered cord release surgeries, considering the possibility of spinal cord tension impacting the flow of CSF ( 35 ).…”