Research & Science

Chiropractic Management of Ehlers-Danlos Syndrome: A Case Report By Joseph J. Morley, DC, PhD;* and Terence Parrault, DC, DACBR*

Address all correspondence to: Terence Perrault, DC, DACBR Associate Professor of Clinical Sciences University of Bridgeport College of Chiropractic 75 Linden Avenue Bridgeport, CT 06604 Tel: (203)-576-4281 E-mail: [email protected]

* Associate Professor of Clinical Sciences, University of Bridgeport College of Chiropractic

ABSTRACT

Objective: To structure chiropractic care for the symptomatic relief of musculoskeletal symptoms in a patient with Ehlers-Danlos Syndrome (EDS).

Clinical Features: A patient with EDS presented with chronic dorsal, neck, and low-back pain. She also had joint hypermobility, skin hyperelasticity and spontaneous glenohumeral dislocations.

Intervention: Treatment included soft-tissue work and chiropractic manipulation. Treatment lasted for 7 months.

Outcome: The patient reported a noticeable reduction in neck, dorsal, and low-back pain during treatment.

Conclusion: Chiropractic care helped relieve some of the more common musculoskeletal symptoms in this patient and may prove of value in other EDS patients. Doctors of chiropractic who are aware of EDS and its associated symptoms may be able to offer significant relief in selected EDS cases. A large-scale trial of chiropractic management of EDS needs to be done to demonstrate efficacy or lack thereof.

Key Indexing Terms: Ehlers-Danlos Syndrome; musculoskeletal pain; chiropractic

INTRODUCTION • deficiencies of enzymes that produce Ehlers-Danlos Syndrome (EDS) is an inherited collagen disorder of connective tissue characterized by • mutation of collagen alpha chains heterogenicity and variance in clinical symptoms.1 Mao2 identifies 3 mechanisms by which Enzyme deficiencies or mutations affecting dif- the disease can occur: ferent collagens involved in EDS will become

6 MARCH 2010 Research and Science manifest in tissues in which that particular type logical problems,10 epilepsy,11 cerebral cortical of collagen predominates functionally, i.e., lesions,12 cephalalgia,13 and musculoskeletal skin, ligament, vascular tissue, bowel tissue, pain.14-16 and oral structures. Previously, Ehlers-Danlos was divided into 10 • Haplo-insufficiency types. This was based on single-gene disorders. More recently, the Villefranche classification This results from a lower level of a gene prod- (Table 1) was developed.17 The Villefranche uct and affects the cell’s ability to function nor- classification categorizes Ehlers-Danlos into 6 mally. groups based on the severity of the clinical features, biochemical defects, genetic defects, and Research has also concentrated on tenascin-X inheritance pattern.1,18 deficiency in connective tissues.3,4 This is an extracellular-matrix protein. However, tenascin-X deficiency is not found in a large per- centage of EDS patients but seems to be associated more with the hypermobility type of EDS.3,5 Malfait suggests that other genetic factors and gender both contribute to EDS. Most of those suffering from the joint hypermobility type of EDS and associated pain were women.1

Fig. 2. Joint hyperflexibility7 Although joint hypermobility may be the most noticeable symptom, skin hyperelasticity, ex- The most common form of EDS is autosomal tensive bruising and scarring, and connective dominant in the older classification, hyper- tissue fragility can be common features. Typi- mobility type in the newer Villefranche classical examples of skin hyperelasticity and joint fication. The major diagnostic criteria are joint hypermobility associated with EDS are seen in hypermobility and skin described as soft, Figs. 1 and 2, respectively. smooth, and velvety. Joint hypermobility can

lead to dislocation, which Beighton17 lists as

one of the minor diagnostic criteria. Other mi-

nor criteria include chronic joint or limb pain

and a positive family history. Beighton17 stated

that one or more of the major criteria must be

present for a definitive clinical diagnosis. Mi-

nor criteria aid in the diagnosis but are not suf-

ficient in themselves.

Fig. 1. Skin hyperelasticity6 A major symptom, joint hypermobility, is also shared with Marfan’s Syndrome, Benign Joint Familial Hypermobility Syndrome, and Osteo- More serious symptoms associated with EDS 19 can include joint dislocations, rupture of blood genesis Imperfecta. The heterogenicity of vessels and hollow viscera, and mitral valve EDS and the fact that symptoms and severity prolapse. Other reported manifestations of EDS can overlap with other conditions can lead to can include periodontal problems,8,9 psycho- difficulty in diagnosis.

JOURNAL OF THE AMERICAN CHIROPRACTIC ASSOCIATION 7 Research and Science CASE REPORT • previous episodes of epileptic seizures, This case study dealt with the hypermobility the last one occurring 2 years ago type of EDS, which may be the type that is • blood loss anemia in the past – heavy characterized by the most functional muscu- menstrual periods and nosebleeds 14 loskeletal problems. • easy bruising • asthma A 5’ 4” 120 lb., 20 year old female college student suffering from chronic spinal pain sought Previous treatments included: evaluation of her condition at a chiropractic • 2 months of physiotherapy for thoracic clinic. and cervical pain immediately following her car accident This patient had been diagnosed with EDS • massage therapy for thoracic and cervi- prior to seeking chiropractic care. Her family cal pain history included a brother also with EDS. She • spontaneous reductions of dislocations reported that he had a more severe form than or self-reductions of shoulder disloca- she did, but did not elaborate any further. Past tions medical history included pyloric stenosis as an • 2 hours of cardiovascular and weight infant and an appendectomy 2 years previously. exercises regularly

• dihydrocodeine for spinal pain Her lifestyle and dietary history revealed that she was a non-smoker, consumed very little • carbamazepine for epilepsy alcohol, had a regular intake of fruits and vege- • sodium valproate for epilepsy tables, and ate chicken in preference to red • phenytoin for epilepsy meats. She did not drink coffee and drank at • beclometasone for asthma least a quart of water per day. She did not re- • salbutamol for asthma port taking any supplements. • iron tablets for blood loss anemia

Her major complaints were thoracic and cervi- Informed consent was obtained from the pa- cal pain that worsened after a car accident 3 tient and a physical examination was per- years ago. Prior to this accident, she had had formed. periodic discomfort in these areas, but not to the extent now reported. She reported the pain General Findings as ranging from 3 to 8 on a 10-point scale. The Vital signs were within the normal range for a spinal pain had become worse recently, tending female of her age. The skin was elastic and toward 8. smooth. A scar was noted at the mid-sternal area and the patient reported that a keloid had Her secondary complaints included repeated been removed years ago. There was hyperex- bilateral shoulder dislocations and hip and fin- tension of both knees, both elbows, over- ger dislocations. Other secondary complaints pronation of the feet, and loss of the normal included: medial longitudinal arches. • difficulty sleeping due to the thoracic and cervical pain Cervical Exam • occasional low-back pain that seemed to Hypolordosis worsen with menstruation, but did not Head anterior to gravity line worsen after the accident Cervical distraction produced some pain radiat- ing toward her right shoulder but not in her neck. Passive bilateral rotation, lateral flexion,

8 MARCH 2010 Research and Science flexion, and extension were negative. An active the legs and arms (biceps and triceps curls, trigger point was found in the right upper tra- knee extensions, squats) and walking and jog- pezius. ging. These exercises are beneficial for maintaining muscle mass, minimizing osteoporosis, Thoracic Exam and maintaining the cardiovascular system in Rotation and lateral flexion were restricted bi- good health. Advice regarding the importance laterally from T5-T10. Active trigger points of Vitamin C for connective tissue was given. were found in the rhomboid majors, thoracic paravertebral musculature bilaterally, and mid- Over a 10-month period, she was seen a total of dle trapezii. 20 times. Within a week, after 3 visits, she reported an improvement of overall pain, down Lumbo-sacral Exam from an 8 to a 4. By the end of the second week Hypolordosis of treatment (visit 5), she reported that her Right SI motion was restricted. Palpation of menstrual period was lighter and shorter than right SI joint elicited tenderness. normal. At visit 6, she reported an exacerbation of thoracic pain, a 7 on the pain scale. At visit Radiological Exam 7, she reported that she had responded to the A radiological report for lumbar, thoracic and last treatment but the thoracic pain had returned cervical x-rays taken elsewhere stated that after a few days. There had been a spontaneous there were no fractures or dislocations. A loss shoulder dislocation and subsequent neck pain of normal cervical lordosis was also reported. on her right side. By visit 9, she had been under care for almost 2 months. She reported a sig- Diagnoses, Rationale, and Treatment nificant reduction in her neck and back pain Exam and history findings supported a diagno- from the last visit until the current visit. Her sis of myofascial pain related to specific trigger pain was at a 2. She also reported that her men- points in the mid and upper trapezii, rhomboid strual periods were shorter and less painful than majors, and thoracic paravertebral muscles. In normal. addition, there was pain associated with fixa- tion of the right SI joint and vertebrogenic pain She was a student and did not return for 2 associated with restriction of movement of T5- months during the summer break. Her symp- T10. toms were at about a 2 or 3 during this period. At the 12th visit, she reported that her cervical Given the above findings, the connective tissue area had been quite sore after the last treatment. characteristics associated with EDS, and the This is an indication of the necessity to ensure non-specific palliative care common for that soft-tissue work and manipulations are not EDS,14,15,19 it was decided to treat this patient done too vigorously. symptomatically, utilizing gentle soft-tissue work and gentle vertebral adjusting. She had By the 14th visit, her symptoms were once reported getting relief from dihydrocodeine, a again reduced to a 3. Symptomatically, she re- drug used for the treatment of musculoskeletal mained at a 2 or 3 for the remainder of her vis- pain.15 This indicated that her symptoms could its. We lost contact with her after she finished be relieved. If relief could be provided with her degree. chiropractic care, the side effects associated with an opioid drug might be avoided. DISCUSSION In general, it is possible to determine the cause She was advised to continue with her exercises. of a patient’s pain following an accident. How- Her regular routine included weight lifting for ever, the superimposition of a motor vehicle

JOURNAL OF THE AMERICAN CHIROPRACTIC ASSOCIATION 9 Research and Science accident on defective connective tissue as seen feet, recurvatum of the knee and congenital hip in EDS complicated the diagnosis. How much dislocation are also findings commonly seen in of the spine-related pain was due to EDS and these patients resulting from joint laxity.21-23 how much was due to the accident cannot be The increased motion found at articulations can determined precisely. We can state that her often result in premature and severe degenera- spine-related pain worsened after the accident. tive changes. The metacarpophalangeal and We can also state that this patient improved interphalangeal joints of the hand may demon- symptomatically under chiropractic care. Al- strate severe degeneration resembling neuro- though one case study does not prove that chi- pathic joints. Acroosteolysis is also a potential ropractic care is an effective treatment for mus- radiographic finding24. culoskeletal symptoms common in EDS, it is a reasonable hypothesis that a trial period of chi- Radiographic findings in the axial skeleton can ropractic care could demonstrate significant include pectus excavatum or carinatum, hy- relief of musculoskeletal pain in EDS as long perkyphosis/hypokyphosis, and scoliosis. Ver- as the complications associated with EDS are tebral body scalloping is also visible. The scal- known. There are several factors that favor this loping is usually along the posterior vertebral approach: body, and is the result of dural ectasia.21, 25 • back and neck pain are common14 However, at least one author suggests lateral • joint pain is common15 scalloping is possibly due to dysplasia.20 • headache is common13,15 Spondylolysis and spondylolisthesis are also • musculoskeletal symptoms start early possible findings in EDS. and get progressively worse15 • current medical treatment is non- Soft-tissue findings may include persistent joint 14,15,19 effusions or hemearthrosis, as well as both ole- specific and palliative 21 • in a survey of EDS patients, chiropractic cranon and prepatellar bursitis. One of the care was one of the treatment methods most common radiographic findings within the used15 soft tissues, occurring in approximately one third of the patients, is small foci of subcutane- • two case studies have been published ous calcification.25 previously that involved chiropractic These small densities usu- 20 ally demonstrate lucent centers and resemble treatment of EDS phleboliths. The calcifications are the result of

either hemorrhage or fat necrosis, and are often Radiographic Findings in EDS seen along the forearms, shins, and extensor The radiographic picture of Ehlers-Danlos syn- surfaces of the extremities.20, 21, 26 drome can be connected, at least in part, with These calcifications should be differentiated from heman- the joint hypermobility and connective tissue/skin manifestations. Due to the increased giomas or certain soft-tissue infections. Other calcifications of the soft tissues may be seen as joint motion, dislocations and subluxations are a result of myositis ossifications or scarring. common. This would present with typical x-ray Heterotropic ossification is also seen in EDS findings of dislocation/subluxation, such as and occurs primarily in the region of the pelvis loss of apposition of articular surfaces, or com- 21 plete disassociation of opposing bones. The and hips . more frequent sites of dislocation include the glenohumeral, and acromioclavicular joints of One unusual manifestation of soft-tissue calcification is detected specifically in the Type IX the shoulder, as well as interphalangeal, patel- lofemoral, sternoclavicular, radiocapitellar, and Ehlers-Danlos syndrome (using the older clas- 21 sification system mentioned in the Introduc- temporomandibular joints. Pes planus of the tion). The radiographic appearance of “occipi-

10 MARCH 2010 Research and Science tal horns,” or horn-shaped excrescences on the occipital bone, is rare to all other categories of Neurology and Nutrition EDS.21,22 The cause of this osseous manifesta- The various types of EDS mainly involve col- tion is unknown. lagen types I, II, III, V and XI.9 Interestingly, muscle spindles are reported to be rich in type- Goal Setting IV collagen, which is not implicated in EDS.27 Goal setting for conditions such as EDS must This would suggest that afferent information take into consideration the heritable nature of from the spindles is normal. However, spindles the disease. Therapy should be designed to are activated by passive stretch. Faulty me- provide temporary relief of symptoms and chanics, such as carrying the head anterior to make the activities of daily living easier to per- the gravity line could also lead to passive form. An added benefit is that success in reduc- stretch of posterior cervical muscles, contribut- ing pain, albeit only temporary, can reduce the ing to aberrant afferent input into the spinal quantity of pain killers that the EDS patient cord. Passive stretch of genetically weak con- may be taking. This point is discussed well by nective tissue could lead to an increase in neck Colloca20 in the previous report of chiropractic pain in this situation. This would justify at- management of EDS. All of this must be ex- tempting to minimize mechanical faults in the plained to the patient so that realistic expecta- EDS patient. Colloca20 points out that the in- tions can be made and false hopes not pro- herent weakness of the connective tissue in moted or assumed. EDS could result in spinal instability, ligamen- tous laxity, and vertebral deformity. Mechani- Exercise/Home Care cal faults, especially in the lower lumbar spine, It was fortunate in this case that the patient was can lead to an increase in shear forces on discs. already committed to daily exercise that in- Given an already weakened connective-tissue cluded both aerobic and weights. One of the condition, increasing shear force can further psychological ramifications of chronic pain is a exacerbate low-back problems in the EDS pa- loss of interest in doing exercises and onset of tient. Joint capsules and ligaments are well depression. Since exercises can help to reduce supplied with mechanoreceptors and proprio- the impact of pain, motivating the EDS patient ceptors.28-30 Inherent weakness in connective to get on a regular program needs to be incor- tissue, as in EDS, means that afferent input porated into the treatment regimen. There is a from joint capsules and ligaments in these pa- sound mechanical reason for doing exercises tients could result in muscle spasm and pain. with weights. Tendons, ligaments, and muscles The chiropractor needs to try to minimize all hypertrophy in response to exercises with faulty biomechanics through exercise and ma- weights. How this can be beneficial is illus- nipulation tailored to the EDS patient to nor- trated by the dimensionless formula for stress: malize afferent input.

There is another type of proprioceptor contained within the muscle, the Golgi tendon organ (GTO). It is located at the junction of the muscle where = stress, F = force, A = area and tendon, and lies in series with the muscle. When stimulated, it can have an inhibitory effect Hypertrophy of muscle, tendon, or ligament on its own muscle and synergists, and an excita- increases its size or area, the denominator A. tory effect on the antagonists. It is stimulated This thus can reduce the force F per unit area slightly by passive stretching. It is also stimu- and can help to minimize mechanical damage lated by the contraction of the muscle. to the affected structure.

JOURNAL OF THE AMERICAN CHIROPRACTIC ASSOCIATION 11 Research and Science The fact that the GTO can have an inhibitory with Vitamin C would seem to be a rational affect on its own muscle may seem contradictory therapeutic choice. at first. However, it acts in coordination with other sensory information, such as that from Redaelli33 did a study in which he demonstrated muscle spindles and mechanoreceptors, to allow that the transfer of force in a tendon is not all for an appropriate response. The self-inhibition due to long tendon fibrils running the entire is a protective mechanism that occurs if the load length of the tendon. There is some evidence on a muscle is so great that a continued that an extra-cellular matrix consisting of contraction would result in tearing or rupture of glycosaminoglycans (GAG) aids in force muscle and/or tendon. transfer. Glucosamine sulfate and chondroitin sulfate are both constituents of GAG. GAG What load on a muscle/tendon arrangement is helps to provide adherence between parallel too great? The same load placed on a normal shorter fibers. This is sufficient to allow for muscle/tendon complex and on a muscle/tendon transfer of force between adjacent fibers and complex in an EDS patient could have different hence through the entire tendon. Mao’s2 consequences due to the inherent weakness of investigation into collagen structure showed connective tissue in EDS. Weakened connective that collagen V is a factor in limiting the tissues are susceptible to damage due to tensile diameter of collagen fibrils. Typical in EDS or shearing forces placed on them or if they are hypermobility type is an increase in fibril required to transfer loads. diameter and the production of rare collagen cauliflowers. The mechanism by which the Mantle et.al.31 have suggested that the inherent defect in collagen V contributes to weakness in EDS connective tissue may be biomechanical instability involves fibril helped somewhat by selected nutritional disarray rather than hyper-extensibility of the support. Vitamin C and glucosamine sulphate collagen fibrils. Whether this cross force are 2 of the nutrients that they discuss. EDS transfer could be helped in EDS patients by connective tissue bears comparison to nutrition emphasizing glucosamine sulfate and connective tissue seen in the classical chondroitin sulfate is not known at this time. nutritional disease, scurvy. A lack of Vitamin Given the promising research of GAG in joint C prevents the formation of normal connective pain and mobility, this may prove to be tissue and leads to the weakening of tendon, beneficial in managing EDS patients.34 ligament and vascular structures. Vitamin C is essential for hydroxylation of the amino acids It is interesting to note the patient reported an proline and lysine, which are necessary steps in improvement in menstrual cramping during her the formation of normal collagen. Shashikiran32 care. Previous research has indicated that lum- reported that Vitamin C supplementation bar spinal manipulation might reduce the resulted in an improvement in collagen cramping and prostaglandin F2a metabolites synthesis in EDS patients suffering from associated with menstrual pain.35 This pros- recurrent respiratory infections. The taglandin factor contributes to smooth muscle Villefranche17 classification of EDS shows that contraction and platelet aggregation, factors the kyphoscoliosis type of EDS (formerly type responsible for the cramping and excessive VI) is characterized by a deficiency of lysyl bleeding often noted during menstruation. hydroxylase. This enzyme is needed for the Prostaglandins are hormone-like substances hydroxylation of lysine and hence normal that are elaborated near or at the site of their collagen formation. Vitamin C is a requirement activity. They can be either pro or anti- for this step. Supplementation of EDS patients inflammatory. There are 3 series of prostaglandins that can be produced in the body;

12 MARCH 2010 Research and Science series 1, 2, or 3. The series depends on the sub- damage.36-38 Soft-tissue work must also be gen- strate of dietary fatty acid intake. Linoleic acid tle due to the hyperelasticity of the skin. Nutri- will produce type 1 prostaglandins, arachidonic tional therapy has yet to be demonstrated to be acid will produce series 2, and linolenic acid effective on a large scale but preliminary re- will produce type 3. Series 3 prostaglandins sults indicate that it is an avenue that needs fur- are the least inflammatory, while series 2 are ther trials. Unfortunately, we did not follow up the most inflammatory. Diet may have a sig- on whether this patient started taking Vitamin nificant role and it may be helpful for the EDS C. Exercise is important and it is here that mo- patient to include oily fish or fish oil supple- tivating patients and frequently encouraging ments in the diet. This type of fat will help the them becomes essential. production of the series 3 prostaglandins and As Colloca20 stated, no definitive conclusions theoretically could minimize inflammation. can be drawn from a case report. However, given the non-specificity of current medical CONCLUSION care and the emphasis on symptomatic relief, Chiropractic management has the potential to chiropractic care could prove to be beneficial help alleviate the pain and mobility restrictions for the EDS patient. It is hoped that a proper that are associated with the hypermobility type large-scale study involving chiropractic and of EDS. Vigorous manipulation must be EDS will be undertaken soon in order to assess avoided given the nature of the connective- this issue. ■ tissue weakness and the potential for vascular

Table 1. Villefranche Classification of types of Ehlers-Danlos Syndromes (reprinted with permission of the author and the publisher)

Type Previous Major Diagnostic Inheritance Nomencla- Minor Diagnostic Criteria Criteria ture Classic Autosomal Types I and Skin hyper- Smooth, velvety skin; easy bruis- dominant II extensibility, ing; molluscoid pseudotumors; wide atrophic scars, subcutaneous spheroids; joint hy- joint hypermobility permobility; muscle hypotonia; postoperative complication (e.g., hernia); positive family history; manifestations of tissue fragility (eg, hernia, prolapse) Hypermobility Autosomal Type III Skin involvement Recurrent joint dislocation; dominant (soft, smooth and vel- chronic joint pain, limb pain, or vety), joint hyper- both; positive family history mobility Vascular Autosomal Type IV Thin, translucent skin; Acrogeria, dominant arterial/intestinal fra- hypermobile small joints; ten- gility or rupture; ex- don/muscle rupture; clubfoot; tensive bruising; char- early onset varicose veins; arte- acteristic facial ap- riovenous, carotid-cavernous si- pearance nus fistula; pneumothorax; gingival recession; positive family history; sudden death in close relative

JOURNAL OF THE AMERICAN CHIROPRACTIC ASSOCIATION 13 Research & Science Kyphoscoliosis Autosomal Type VI – Joint laxity, severe hy- Tissue fragility, recessive lysyl hypotonia at birth, scolio- easy bruising, arterial rupture, droxylase sis, progressive scleral marfanoid, deficiency fragility or rupture of microcornea, globe osteopenia, positive family history (affected sibling) Arthrochalasia Autosomal Type VII A, Congenital bilateral Skin hyperextensibility, dominant B dislocated hips, tissue fragility with atrophic scars, severe joint hyper- muscle hypotonia, mobility, easy bruising, recurrent subluxations kyphoscoliosis, mild osteopenia Dermatosparaxis Autosomal Type VII C Severe skin fragility; Soft, doughy skin; recessive saggy, redundant skin easy bruising; premature rupture of membranes; hernias (umbilical and inguinal)

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