Research Article
Open Access
Dystonia in the joint hypermobility syndrome (a.k.a. Ehlers-
Danlos syndrome, hypermobility type)
Hamonet C1,2*, Ducret L3, Marie-Tanay C4, Brock I2
1Assistant Professor, Department of Pediatric Neurosurgery, National Institute of Neurosciences & Hospital, Dhaka
1Professeur emeritus Professor, Medical School of Créteil, University Paris-East-Creteil, 8 rue du General Sarail, 91010 Creteil, France
2Ehlers-Danlos Consultation, Hotel-Dieu de Paris, 1 place du Parvis Notre-Dame, 75181, cedex 04 Paris
3Department of Dermatology, Hopital Tarnier, 89 rue d'Assas, 75006, Paris
4Health Center of Argouges, rue de Beauvais, 14400 Bayeux
1Professeur emeritus Professor, Medical School of Créteil, University Paris-East-Creteil, 8 rue du General Sarail, 91010 Creteil, France
2Ehlers-Danlos Consultation, Hotel-Dieu de Paris, 1 place du Parvis Notre-Dame, 75181, cedex 04 Paris
3Department of Dermatology, Hopital Tarnier, 89 rue d'Assas, 75006, Paris
4Health Center of Argouges, rue de Beauvais, 14400 Bayeux
*Corresponding author: Hamonet C, Professeur éméritus Professor, Médical School of Créteil, University Paris-East-Creteil, 8 rue du Général Sarail, 91010
Créteil, France; Ehlers-Danlos Consultation, Hôtel-Dieu de Paris, 1 place du Parvis Notre-Dame, 75181, cedex 04 Paris E-mail:
@
Received: January 01, 2016; Accepted: February 04, 2016; Published: Feburary 29, 2016
Citation: Hamonet C, Ducret L, Marié-Tanay C, Brock I (2016) Dystonia in the joint hypermobility syndrome (a.k.a. Ehlers-Danlos
syndrome, hypermobility type). SOJ Neurol 3(1), 1-3. DOI: 10.15226/2374-6858/3/1/00123
AbstractTop
Ehlers-Danlos syndrome first described by Tschernogobow
(1896) in Moscow and Ehlers (1900) in Copenhagen is a mostly
autosomal inherited genetic disease of collagen synthesis that
sensitizes the ensemble of the connective tissue which becomes
less resistant and less elastic. These two characteristics explain the
symptomatology: fragility of the skin, of the vessels (haemorrhages)
and the presence of a diffuse proprioceptive syndrome due to
dysfunction of the receptors which are implanted into little or nonreactive
connective tissue. Diagnosis of the hypermobile type of EDS
is solely clinical as there is to date no genetic maker for the most
frequent form of EDS. The rarity of the disease needs to be put into
question before the crowd of patients at consultations. Our experience
is based on an active database of 2212 patients which all fall under
the Villefranche criteria. A great number of signs and symptoms
have yet to be attributed to this syndrome. They are, combined with
the unawareness of physicians about the syndrome, at the origin of
therapeutic errors accompanied by the iatrogenic effects of prejudice
towards these patients. This is the case of dystonia which is present in
75% of our cases. Dystonia plays an important part in the functional
discomfort which is at the origin of a number of handicap situations.
It seems to be related to dysautonomia common amongst the patients,
proprioceptive problems and the multiple pains caused by the
syndrome. Dystonia treatment with Amantadine and L-Dopa permits
to obtain results which go further than the normally associated extrapyramidal
treatment and opens new perspectives on the management
of a syndrome that has been particularly difficult to treat.
Keywords: Ehlers-Danlos syndrome (EDS); Dystonia; Dysautonomia; L-dopa; Pains; Fatigue
Keywords: Ehlers-Danlos syndrome (EDS); Dystonia; Dysautonomia; L-dopa; Pains; Fatigue
Introduction
Ehlers-Danlos syndrome (EDS) recognition went through
many vicissitudes since the first outstanding description by
Tschernogobow [1] and Ehlers [2] respectively in Moscow in
1896 and in Copenhagen in 1900. EDS' genetic grounds have been
recognized since 1949 [4] collagens role as early as 1956 [5]. EDS was studied in parallel by the rheumatologists (Brighton and
Grahame) and the geneticist (Beighton) who is working mainly
on articular hypermobility with different assessment tests.
There is perfect similarity between the rheumatologists' joint
hypermobility syndrome and the geneticists' EDS hypermobility
type. These two denominations refer in fact to the same illness.
However, a great body of clinical manifestations has not yet been
assigned to this syndrome. They are, in combination with the
physicians' usual unawareness of this syndrome, the cause of
many diagnostic wavering with their iatrogenic side-effects that
harm the patients. This is the case with dystonia.
Material and Methods
2,212 patients were diagnosed and followed up in the Ehlers-
Danlos consultation in Paris, between 2006 and 2015. They were
all examined by the same physician with the same evaluation grid
both qualitative and quantitative allowing to rate from 0 to 4 the
symptoms' subjective severity and objective data from clinical
examination. The population's age varies from 2years to 69 years
(mean age: 32). 80% are women.
Inclusion criteria
All the patients in this study met the criteria of the geneticians'
Villefranche classification [6].
On top of the criteria within this classification, we observed a group of 153 patients examined in 2013 with a quotation of severity equal or superior to 2/4 (medium intensity) with clinical manifestations of the following: multiple pains (95%), fatigue (93%), proprioceptive problems (92%), hemorrhages (93%), GERD (72%), bucco-dental manifestations (72%), hyperacousia (75%), diplopia (74%), SOB (76%), dysautonomia: heavy sweating (70%), cold intolerance (74%), a pseudo Raynaud with cold extremities (84%), cognitive problems : attention (79%) and memory (72%). As of date there is no genetic test available for the hypermobile form of EDS. Finding other cases amongst the patient's family (95%) is a strong diagnostic argument.
On top of the criteria within this classification, we observed a group of 153 patients examined in 2013 with a quotation of severity equal or superior to 2/4 (medium intensity) with clinical manifestations of the following: multiple pains (95%), fatigue (93%), proprioceptive problems (92%), hemorrhages (93%), GERD (72%), bucco-dental manifestations (72%), hyperacousia (75%), diplopia (74%), SOB (76%), dysautonomia: heavy sweating (70%), cold intolerance (74%), a pseudo Raynaud with cold extremities (84%), cognitive problems : attention (79%) and memory (72%). As of date there is no genetic test available for the hypermobile form of EDS. Finding other cases amongst the patient's family (95%) is a strong diagnostic argument.
Dystonia identification
Dystonia was diagnosed if a patient suffered from one or
several of the following symptoms:
- Involuntary muscular contractions without movement such as fasciculation on the face, blepharospasm mainly, on the thigh, reminding of a mobile phone vibration in a trouser pocket,
- Sudden movements such as a fit of the wrist, the shoulders, the legs or wide movements which results in hitting objects or people or throwing off balance the patient for whom they occur in the lower limbs
- Trembling, jerking, hesitant hand movements
- Trembling fingers or thumbs in motion or at rest
- Muscular contractions often described as hardening of muscles, rigidity, constraining movement, or as cramps
- Lasting contractions in forced flexion of the thumb or fingers, in flexion and adduction of the feet,
- Writer's cramp when writing after variable amounts of time,
- Incessant, repetitive movement in flexion or extension of the foot and knee when sitting with feet on the ground,
- Repetitive movement of the trunk alternating between flexion and extension at the hip
- Diffuse tonic crises at the lower limbs with alternating, violent movements worsened by tenting to immobilize them
- Short contractions of the lower limbs leading to a fall
- Partial or generalized tonic-clonic movements and the possibility of hematomas facilitated by the fine skin and the fragility of the vessels. These can be confused with seizure activity but the EEG remains normal
- Restless leg syndrome at night, which sometimes evolves into very violent jerks
- Bruxism, which we often encounter in EDS patients could be related to dystonia
- Involuntary muscular contractions without movement such as fasciculation on the face, blepharospasm mainly, on the thigh, reminding of a mobile phone vibration in a trouser pocket,
- Sudden movements such as a fit of the wrist, the shoulders, the legs or wide movements which results in hitting objects or people or throwing off balance the patient for whom they occur in the lower limbs
- Trembling, jerking, hesitant hand movements
- Trembling fingers or thumbs in motion or at rest
- Muscular contractions often described as hardening of muscles, rigidity, constraining movement, or as cramps
- Lasting contractions in forced flexion of the thumb or fingers, in flexion and adduction of the feet,
- Writer's cramp when writing after variable amounts of time,
- Incessant, repetitive movement in flexion or extension of the foot and knee when sitting with feet on the ground,
- Repetitive movement of the trunk alternating between flexion and extension at the hip
- Diffuse tonic crises at the lower limbs with alternating, violent movements worsened by tenting to immobilize them
- Short contractions of the lower limbs leading to a fall
- Partial or generalized tonic-clonic movements and the possibility of hematomas facilitated by the fine skin and the fragility of the vessels. These can be confused with seizure activity but the EEG remains normal
- Restless leg syndrome at night, which sometimes evolves into very violent jerks
- Bruxism, which we often encounter in EDS patients could be related to dystonia
These dystonic contractions provoke luxations of the
shoulder, fingers, a hip, knee or the maxilla. They are most
commonly of short duration but can prolong over several days,
weeks, months or exceptionally years as we have observed in a
few cases.
Dystonia is associated with the accentuation of other manifestations of the syndrome. Pain often increases to a very intense level in the part of the body where the dystonia occurs. Dysautonomic problems (vasomotor, sweating, tachycardia, orthostatic hypotension, freezing and cold intolerance, nausea, sensations of generally feeling unwell, POTS) at which Jaime Bravo [7] attaches fatigue. Pain itself can also provoke dystonia sometimes due to subcutaneous or intramuscular injections, traumatism, or simply during physical exam manoeuvre. It is perceived as painful by these hyperalgesic patients.
Dystonia exists in 75% of our patients with the following severity index: 2/4 (39%), 3/4 (29%) and 4/4 (7%).
Dystonia is associated with the accentuation of other manifestations of the syndrome. Pain often increases to a very intense level in the part of the body where the dystonia occurs. Dysautonomic problems (vasomotor, sweating, tachycardia, orthostatic hypotension, freezing and cold intolerance, nausea, sensations of generally feeling unwell, POTS) at which Jaime Bravo [7] attaches fatigue. Pain itself can also provoke dystonia sometimes due to subcutaneous or intramuscular injections, traumatism, or simply during physical exam manoeuvre. It is perceived as painful by these hyperalgesic patients.
Dystonia exists in 75% of our patients with the following severity index: 2/4 (39%), 3/4 (29%) and 4/4 (7%).
The treatment of dystonia within EDS
Our therapeutic approach of EDS [8] centres on the
amelioration of the proprioceptive troubles, of the pain as well
as the fatigue. Foremost we use proprioceptive shoe inlays and
particularly proprioceptive clothing specifically adapted for
EDS, derived from the treatment of burn victims and oxygen
therapy against fatigue, shortness of breath and migraines. For
the last five years we have successfully used Amantadine after
the discussion with Pierre Cesaro (neurologist, specialist in the
treatment of Parkinson) [9].
When it was taken of the market in France we sought to replace it with L-Dopa which we prescribe at a low dosage (62, 5 mg q3d –Modopar: 50mg L-Dopa +12,5mg Benserazide hydrochloride) adjusted to the needs of the patient especially in severe cases.
We describe here the case of a 54 year old woman, a family medicine physician, who had been diagnosed with EDS-HT. Signs present since childhood worsened at the age of 52: muscular pain, intense fatigue, proprioceptive problems manifesting most importantly with difficulties waling. Signs of dystonia could be observed in the lower limbs. She is very tired with crises of somnolence that disturb her professional life. The fatigue and muscular pain is partially alleviated by wearing proprioceptive shoe inlays, 3 sessions of oxygen therapy (3L/min) 20min/day, baclofen and L-Carnitine.
The effects alleviate progressively over the course of 2 months a generalised sensation of muscular rigidity of the legs and face with difficulties in the articulations, muscular twitches increasing in frequency. She started progressively on a treatment with Modopar (62,5mg q3d). The results were spectacular; after 2 weeks she recuperated fluid motion in her legs, the involuntary muscular contractions disappeared, but there was also improvement in her vigilance and in the fatigue. She stopped the Baclofen without forfeiting anything in her muscular state. After 4 months of the treatment with L-Dopa the effects on her vigilance are maintained with the total loss of the hypersomnia. She can cut down her intake of Tramadol extended release threefold. Whereas before she thought about stopping all of her professional activities, she is now able to pursuit her professional life with efficacy. The oxygen therapy is maintained as well as the L-Carnitine for their action on muscles, because cutting down this part of the treatment lead to an increase in muscular pain.
When it was taken of the market in France we sought to replace it with L-Dopa which we prescribe at a low dosage (62, 5 mg q3d –Modopar: 50mg L-Dopa +12,5mg Benserazide hydrochloride) adjusted to the needs of the patient especially in severe cases.
We describe here the case of a 54 year old woman, a family medicine physician, who had been diagnosed with EDS-HT. Signs present since childhood worsened at the age of 52: muscular pain, intense fatigue, proprioceptive problems manifesting most importantly with difficulties waling. Signs of dystonia could be observed in the lower limbs. She is very tired with crises of somnolence that disturb her professional life. The fatigue and muscular pain is partially alleviated by wearing proprioceptive shoe inlays, 3 sessions of oxygen therapy (3L/min) 20min/day, baclofen and L-Carnitine.
The effects alleviate progressively over the course of 2 months a generalised sensation of muscular rigidity of the legs and face with difficulties in the articulations, muscular twitches increasing in frequency. She started progressively on a treatment with Modopar (62,5mg q3d). The results were spectacular; after 2 weeks she recuperated fluid motion in her legs, the involuntary muscular contractions disappeared, but there was also improvement in her vigilance and in the fatigue. She stopped the Baclofen without forfeiting anything in her muscular state. After 4 months of the treatment with L-Dopa the effects on her vigilance are maintained with the total loss of the hypersomnia. She can cut down her intake of Tramadol extended release threefold. Whereas before she thought about stopping all of her professional activities, she is now able to pursuit her professional life with efficacy. The oxygen therapy is maintained as well as the L-Carnitine for their action on muscles, because cutting down this part of the treatment lead to an increase in muscular pain.
Discussion
Identifying dystonia as a frequent and evocative
manifestation of EDS
Dystonia should be looked for in any patient diagnosed with
EDS. It even contributes to its diagnosis. On the other hand, when
dystonia is present in a patient often associated with psychiatric problems one should think of the possibility of EDS as a diagnosis
and inquire about the other evocative signs: diffuse overall
pain, fatigue, hypermobility, cutaneous fragility, joint problems,
hemorrhages and familial cases.
Reflections on the pathophysiology
We estimate that the alteration in proprioception plays
a large part in the clinical manifestation of EDS. The receptors
placed in a more elastic tissue, diminished in its thickness, easily
deformed and compressed, having lost their elasticity (with a
loss or attenuation of the elastic recoil),which do not or not well
(not enough or too much) to solicitations. This is particularly true
for the skin, which is the most important organ for the postural
proprioception and for movement. This is also very true for the
control of muscular activity via neuromuscular connections.
This receptor dysfunction is also a plausible explanation for the
anarchy within the autonomic nervous system, especially the
crises of tachycardia and hypotension due to a loss in reactivity
of the carotid sinus receptors implanted in altered collagen. This
explanation can be expanded towards the mechanism causing
dyspnea at effort, as the mechanoreceptors of the joints do not
transmit the proper signals to the respiratory centers. One of
the arguments in favor of this explanation is the positive effect
special compressive clothing has on the proprioceptive control of the limbs (less falls, fewer luxation of the shoulder and fingers)
and the improvement of the respiratory difficulties when wearing
these clothes on the trunk. It is logical to interpret dystonia by
way of the same mechanism and the poor information which is
received by the specialized area of central nervous system. The
positive effect observed by Roland Jaussaud [10] on a patient
presenting with permanent, multiple, involuntary movements
which completely ceased after starting to wear the special EDS
compressive clothing. An association between dystonia and
dysautonomia has often been made [11]. This corresponds to our
observations made in consultation, especially in the instances
that our patients came to call "their EDS crises". These crises are
often accompanied by postural orthostatic hypotension (POTS)
which plays an important role in the sensation of fatigue [7, 12].
They are habitually painful, even very painful. These observations
suggest an intricate pathophysiological relationship between
dystonia, dysautonomia and pain in Ehlers-Danlos syndrome
which become the main therapeutic focus.
How to treat dystonia in EDS?
The treatment of the proprioceptive problems (clothes and
inlays), of the pain (inlays, local treatments to be preferred over
the general route), of the fatigue (mostly oxygen therapy) and
of the autonomic dysfunction by way of beta-blockers at low
dose [13] seems to be a necessary prerequisite to be adjusted
towards each patient individually. The specific treatment with
anti-Parkinson medications have mostly been followed by
their effects included on their effects in grand dystonic crises.
The observation of positive effects outside of dystonia bears
two questions: Firstly the role of dystonia itself on fatigue by
way of less muscular activity and a better automatic control of
movement, but also the role of dopamine as a molecule itself in
this systemic disease.
Conclusions
Manifestations of dystonia in EDS is an important adjunct
to further diagnosis and treatment, the understanding of its
pathophysiology of this complex disease, which is little or poorly
diagnosed, altering considerably life quality of the patients
suffering from it and a source of many disabling situations.
The integration of all the manifestations of dystonia into the symptomatology of EDS enriches the clinic of this syndrome and furthers/advances new therapeutic perspectives in a particularly hard to treat pathology. L-Dopa seems to have positive effects that transcend those researched on dystonia itself.
The integration of all the manifestations of dystonia into the symptomatology of EDS enriches the clinic of this syndrome and furthers/advances new therapeutic perspectives in a particularly hard to treat pathology. L-Dopa seems to have positive effects that transcend those researched on dystonia itself.
- Tschernogobow A, Cutis Laxa. Dermatologic and Venereology Society, Nov 13 (1891). Monatshefte für Praktische Dermatologie. 1892;14:76.
- Ehlers E, Cutis laxa. Neigung zu Haemorrhagien in der Haut, Lockerung mehrerer Artikulationen (case for diagnosis), Dermatologishe Zeitschrift. 1901;8:173-174.
- Johnson SAM, Falls HF. Ehlers-Danlos syndrome. A clinical and genetic study. Archives of Dermatology and Syphilology. 1949;60(1):82-105. doi:10.1001/archderm.1949.01530010085006.
- Jansen LH. Le mode de transmission de la maladie d'Ehlers-Danlos. Journal de génétique humaine, 1954;204–218.
- Tinkle BT, Bird HA, Grahame R, Lavallee M, Levy HP, Sillence D. The lack of clinical distinction between hypermobility type of Ehlers-Danlos syndrome and the joint hypermobility syndrome. Am J Med Denet A. 2009; 149A (11):2368-2370.
- De Paepe A, Steinmann B, Tsipouras P, Wenstrup RJ. Ehlers-Danlos syndromes: revised nosology, Villefranche, 1997. Ehlers-Danlos National Foundation (USA) and Ehlers-Danlos Support Group (UK). Am J Med Genet. 1998;77(1):31-37.
- Bravo JF. Elhers-Danlos syndrome (EDS), with special emphasis in the joint hypermobile syndrome. Revista medica de Chile. 2010;137(11):1488-1497. doi: /S0034-98872009001100013.
- Hamonet C. Ehlers- Danlos Syndrome (EDS), a new clinical description, efficiency of physical medicine and rehabilitation. Six hundred individuals, of Physical and Rehabilitation Medicine. 2011;54 suppl-1:e173.
- Hamonet C., Césaro P. Syndrome d'Ehlers-Danlos et dystonie. Effet positif de l'Amantadine, La Presse médicale. 2014;43(9):1017-1018.
- Jaussaud R. Premier colloque international francophone, les traitements du syndrome d'Ehlers-Danlos. Université Paris-Est-Créteil. 2015.
- Rowe PC, Barron DF, Calkins H, Maumenee IH, Tong PY, Geraghty MT. Orthostatic intolerance and chronic fatigue syndrome associated with Ehlers-Danlos syndrome. J Pediatr. 1999;135(4):494-499.
- Bravo J. Dysautonomia in EDS-III, Premier colloque international francophone, les traitements du syndrome d'Ehlers-Danlos, Université Paris-Est-Créteil. 2015.
- Amoretti R. Le cardiologue face au syndrome d'Ehlers-Danlos, Premier colloque international francophone, "les traitements du syndrome d'Ehlers-Danlos", Université Paris-Est-Créteil. 2015