New CCI Research: Understanding the Frequency of Neurosurgical Interventions in Connective Tissue Disorders

A recent study conducted by Ruhoy et al. investigates the frequency of comorbidities and the need for neurosurgical interventions in individuals with connective tissue disorders (CTDs), offering valuable insights into the multifaceted challenges faced by this patient population.

What’s the study about?

CTDs are a diverse group of disorders that impact connective tissue, leading to a wide range of clinical symptoms and comorbidities. Among all CTDs, hypermobile Ehlers-Danlos syndrome (hEDS) is one of the most common, affecting an estimated 1 in 500 people. Individuals with hEDS often experience additional comorbid conditions, such as postural orthostatic tachycardia syndrome (POTS), mast cell activation disorder (MCAD), and craniocervical instability (CCI), highlighting the complexity of their healthcare needs.

In this study, Ruhoy and colleagues aimed to assess the frequency of comorbid conditions and the need for neurosurgical interventions in individuals referred for evaluation of CTDs at their institution. A total of 717 patients were included in the study, with 460 diagnosed with hEDS and 426 diagnosed with Chiari Malformation (CMI).

What did the researchers find?

The study revealed that individuals with CTDs, especially hEDS, often present with multiple overlapping comorbidities. The results showed that 89% of the cohort had either a diagnosis of hEDS, CMI, or both. Among the most common comorbid conditions were:

Tethered Cord Syndrome (TCS) – 42%
Postural Orthostatic Tachycardia Syndrome (POTS) – 41%
Mast Cell Activation Disorder (MCAD) – 34%
Dysautonomia – 27%
Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) – 22%
Styloid Hypertrophy (SH) – 20%
Gastroesophageal Reflux Disease (GERD) – 16%
Hypothyroidism – 14%
Gastroparesis – 12%
Small Fiber Peripheral Neuropathy (SFPN) – 11%
Post-Treatment Lyme Disease Syndrome (PTLDS) – 7%
Mesenteric Artery Ligament Syndrome (MALS) – 5%

Notably, individuals with hEDS were significantly more likely to present with dysautonomia, gastroparesis, MCAD, POTS, SFPN, GERD, TCS, SH, hypothyroidism, ME/CFS, and PTLDS. On the other hand, individuals in the “unaffected” group (those who did not carry a formal CTD diagnosis) were more likely to present with CMI and MALS, suggesting the presence of other undiagnosed congenital syndromes in this population.

What did the study find about intersecting diagnoses?

The study also visualized the intersections of diagnoses, illustrating how multiple conditions intersect across the patient population. The top five patterns of intersecting diagnoses among individuals in the cohort were:

1. CMI in individuals unaffected by CTD (13% of the total cohort)

2. CMI in individuals with hEDS (4%)

3. CMI and TCS in unaffected individuals (3%)

4. Individuals with hEDS (3%)

5. CMI and TCS in individuals with hEDS (3%)

These patterns further emphasize the complexity of the conditions and the importance of a holistic diagnostic approach.

What types of surgeries did the individuals undergo?

A total of 612 individuals (85%) from the cohort had surgery. The most common surgeries included:

Craniocervical Fusion (CCF) – 52%
Posterior Fossa Decompression (PFD) – 44%
Tethered Cord Release (TCR) – 34%
Ventriculoperitoneal Shunt (VPS) – 11%
Styloidectomy – 9%
Cerebrospinal Fluid (CSF) leak repair – 8%
Anterior Cervical Discectomy and Fusion (ACDF) – 6%
Transtemporal Ocular Oculomotor (TOO) – 2%

Of the 460 individuals diagnosed with hEDS, 404 (88%) chose surgical intervention. Among them, 73% required Craniocervical Fusion (CCF) due to craniocervical instability, and 48% sought Posterior Fossa Decompression (PFD).

For individuals presenting with both hEDS and CMI, the most frequent surgical interventions were:

1. Both CCF and PFD (16%)

2. PFD alone (12%)

3. CCF, PFD, and TCR (12%)

4. CCF alone (9%)

Compared to unaffected individuals, those with hEDS had significantly higher rates of certain neurosurgical interventions, including CCF, Styloidectomy, TCR, CSF leak repair.

Key Findings

Comorbidity Clusters: Most individuals in the cohort had either hEDS or CMI, or both. These conditions were often associated with other comorbidities like musculoskeletal, immunological, and autonomic deficiencies.
Surgical Interventions:
- hEDS was associated with a variety of neurosurgical issues, particularly tethered cord syndrome (TCS) and structural compromise of the craniocervical junction (CCJ), requiring interventions like craniocervical fusion (CCF).
- CMI also required surgical intervention, but the profile of surgeries differed, with more frequent interventions like PFD, VPS, ACDF, and TOO.
Overlapping Pathologies: The study confirmed that hEDS and CMI are often co-occurring conditions. Over half of those diagnosed with one of these also presented with the other, indicating that they may share pathophysiological mechanisms. However, despite this overlap, the specific types of surgeries required for each condition were distinct.
Gender and Autonomic Dysfunction: The study found a significant gender skew, with females being the predominant group in this cohort. It also noted high rates of autonomic dysfunction (like POTS) and immune-related comorbidities (such as MCAD) in individuals with hEDS. These conditions are often found together, forming a diagnostic triad that requires surgical attention for related issues such as CCF, TCR, and CSF leaks.
Additional Associations:
- Individuals with hEDS had elevated rates of comorbid conditions like gastroparesis, MALS, dysautonomia, SFPN, GERD, hypothyroidism, ME/CFS, and PTLDS. These were much more common in the hEDS group than in those with CMI.
- The study suggests that future diagnostic procedures should account for these associated comorbidities, as they often cluster together in patients, requiring multifaceted management.

What does this mean for patients with CTDs?

The findings suggest that the individuals in this cohort rarely fit into a single diagnostic category, but rather form clusters of comorbidities. This complexity necessitates a comprehensive approach to diagnosis and treatment. Additionally, there is a clear need for neurosurgical intervention in many individuals with CTDs, particularly hEDS, due to the structural and neurophysiological dysfunctions associated with connective tissue laxity. These interventions often address both the structural issues (e.g., CCJ instability) and other neurophysiological complications (e.g., CSF leaks, TCS). Moreover, the study suggests that clinicians should be aware of the wide range of comorbidities associated with hEDS and CMI when evaluating and treating patients. Comprehensive diagnostics may improve patient outcomes by addressing the full spectrum of these conditions.