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Journal of Parkinson’s Disease xx (20xx) x–xxDOI 10.3233/JPD-160836IOS Press

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Review1

Pathophysiological Concepts and Treatmentof Camptocormia

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N.G. Margrafa,∗, A. Wredeb, G. Deuschla and W.J. Schulz-Schaefferb,∗4

aDepartment of Neurology, University Hospital Schleswig-Holstein, Campus Kiel, Germany5

bInstitute of Neuropathology, University Medical Center, Gottingen, Germany6

Accepted 17 May 2016

Abstract. Camptocormia is a disabling pathological, non-fixed, forward bending of the trunk. The clinical definition usingonly the bending angle is insufficient; it should include the subjectively perceived inability to stand upright, occurrence ofback pain, typical individual complaints, and need for walking aids and compensatory signs (e.g. back-swept wing sign).Due to the heterogeneous etiologies of camptocormia a broad diagnostic approach is necessary. Camptocormia is mostfrequently encountered in movement disorders (PD and dystonia) and muscles diseases (myositis and myopathy, mainlyfacio-scapulo-humeral muscular dystrophy (FSHD)). The main diagnostic aim is to discover the etiology by looking for signsof the underlying disease in the neurological examination, EMG, muscle MRI and possibly biopsy. PD and probably myositiccamptocormia can be divided into an acute and a chronic stage according to the duration of camptocormia and the findings inthe short tau inversion recovery (STIR) and T1 sequences of paravertebral muscle MRI. There is no established treatment ofcamptocormia resulting from any etiology. Case series suggest that deep brain stimulation (DBS) of the subthalamic nucleus(STN-DBS) is effective in the acute but not the chronic stage of PD camptocormia. In chronic stages with degenerated muscles,treatment options are limited to orthoses, walking aids, physiotherapy and pain therapy. In acute myositic camptocormia anescalation strategy with different immunosuppressive drugs is recommended. In dystonic camptocormia, as in dystoniain general, case reports have shown botulinum toxin and DBS of the globus pallidus internus (GPi-DBS) to be effective.Camptocormia in connection with primary myopathies should be treated according to the underlying illness.

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Keywords: Camptocormia, bent spine syndrome, stooped posture, postural abnormality, back pain22

DEFINITION OF CAMPTOCORMIA23

Camptocormia (from the Greek “kamptein” = to24

bend and “kormos” = trunk) is an involuntary flexion25

of the thoracolumbar spine when standing, walking26

or sitting, which disappears completely in the supine27

∗Correspondence to: Nils G. Margraf, MD, Mpsych, Depart-ment of Neurology, University Hospital Schleswig-Holstein,Campus Kiel, Arnold-Heller-Str. 3, 24105 Kiel, Germany.Tel.: +49 431 5978807; Fax: +49 431 5978502; E-mail:n.margraf@neurologie.uni-kiel.de and Walter J. Schulz-Schaeffer,MD, PhD, Prion and Dementia Research Unit, Institute ofNeuropathology, University Medical Center Goettingen, Robert-Koch-Str. 40, 37075 Goettingen, Germany. Tel.: +49 551 3922707; Fax: +49 551 39 10800; E-mail: wjschulz@med.uni-goettingen.de.

position. The syndrome is also known as “bent spine 28

syndrome”, was first described by Henry Earle in 29

1815 [1] and reported by James Parkinson in some 30

of his cases in 1817 [2]. The term was coined by the 31

French neurologist A. Souques in 1915 to describe an 32

“incurvation du tronc” in soldiers of World War I indi- 33

cating a “cyphose hysterique” [3]. Until the 1980 s, 34

camptocormia was considered to be a psychiatric con- 35

dition. Kiuru & Iivanainen [4] and Laroche et al. [5] 36

were the first to describe camptocormia in association 37

with organic diseases. 38

The criteria for defining camptocormia are a matter 39

of debate. Most studies use a forward bending angle 40

of between 15◦ to 45◦ as the main criterion [6–17]. 41

A large number of studies use only a descriptive 42

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This article is published online with Open Access and distributed under the terms of the Creative Commons Attribution Non-Commercial License.

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2 N.G. Margraf et al. / Pathophysiology and Treatment of Camptocormia

term without a bending angle, indicating the diffi-43

culties in defining camptocormia [18–28]. Based on44

a control group of patients with Parkinson’s disease45

(PD) who disclaimed suffering from camptocormia,46

a recent study demonstrated that the stooped pos-47

ture of advanced PD does not exceed a forward48

bending angle of 25◦. Oeda et al. found a similar49

forward bending angle distribution in PD patients50

without camptocormia [29]. Furthermore, analysis of51

the group of photo-documented PD camptocormia52

patients (n = 145) showed that the bending angle as the53

sole criterion is insufficient to define camptocormia54

[Margraf et al., 2016 under review] because a third of55

the patients who suffered subjectively from campto-56

cormia had an angle of less than 30◦.57

Others have defined camptocormia by a score58

of ≥ 2 of item 28 (posture) of the Unified Parkinson59

Disease Rating Scale part III (UPDRS III) [30]. This60

definition does not differentiate between the stooped61

posture of advanced PD and camptocormia. Even the62

revised MDS-UPDRS item “posture” (3.13) cannot63

differentiate between stooped posture and campto-64

cormia. The ability of a patient to straighten up65

temporarily does not rule out camptocormia and for-66

ward bending by orthopedic diseases of the spine67

must be excluded.68

As camptocormia is a very disabling syndrome that69

frequently causes social isolation of patients [13], the70

diagnosis of the syndrome may be supported by typ-71

ical individual complaints resulting from the loss of72

function of paraspinal muscles [31]. Characteristic73

complaints are the inability to drive a car (because of74

the inability to turn the body backwards), inability to75

look people in the eyes, inability to carry something76

in front of the body, inability to pick up things that77

lay higher than the table or the shoulder position and78

problems in eating and swallowing or dyspnoea due79

to body position (Margraf et al., 2016 under review).80

In summary, camptocormia is an involuntary81

pathological flexion of the thoracolumbar spine that82

is passively reversible (recumbent position) and that83

causes relevant impairment in daily life as well as84

back pain in most cases. The definition and the clini-85

cal diagnostic criteria should focus on the following86

aspects: Involuntary flexion of the thoracolumbar87

spine, reversibility in recumbent position, forward88

bending angle, individual complaints, back pain,89

hardening of the paraspinal muscle and the course90

during the day.91

Camptocormia is unlikely to be confused with the92

dropped-head syndrome, even when these two occur93

together in rare instances [32]. A relevant number94

of PD camptocormia patients present with additional 95

laterodeviation [8, 10, 31], but there are no accepted 96

criteria of how to differentiate the combination of 97

Pisa syndrome and camptocormia. Seen pragmati- 98

cally, the predominant abnormality gives the name 99

but the underlying abnormality may be the same. 100

OCCURRENCE OF CAMPTOCORMIA 101

Camptocormia occurs in association with primary 102

and secondary myopathies, inflammation, dystonia, 103

as a pharmacological side effect or as a functional 104

disorder. Primary muscle diseases with involve- 105

ment of axial muscles, focal myositis and secondary 106

myopathies associated with neurodegenerative dis- 107

eases seem to be the most frequent causes of 108

camptocormia. The overall incidence of campto- 109

cormia is unknown. Data on the incidence have only 110

been published for movement disorders. The rela- 111

tive frequency of primary or secondary myopathies or 112

focal myositis varies with the specialty of the report- 113

ing departments. In a cohort of camptocormia patients 114

from a rheumatology center, 65% of the patients suf- 115

fered from a dystrophy, 17% from PD and 13% from 116

a myositis [33]. In a cohort from a neuromuscular 117

center, 25% suffered from a facio-scapulo-humeral 118

muscular dystrophy (FSHD) and 18% from sporadic 119

inclusion body myositis [32]. There is some evidence 120

that FSHD is underdiagnosed in camptocormia [34]. 121

Camptocormia occurs in a broad range of primary 122

muscle diseases. It can be due to dystrophies, espe- 123

cially FSHD, limb-girdle dystrophies and myotonic 124

dystrophy, structural myopathies and metabolic 125

myopathies including defects in energy metabolism 126

and hypothyroidism. It may occur in all forms of 127

inflammatory muscle diseases. Camptocormia may 128

occur in diseases of the neuromuscular junction, espe- 129

cially myasthenia gravis and as radiation-induced 130

secondary myopathy. In some patients, degenerative 131

changes of the spinal column may cause campto- 132

cormia [35]. A list of underlying diseases is given 133

in Table 1. 134

Among neurodegenerative diseases, campto- 135

cormia occurs most frequently in PD [6]. The 136

published prevalence rates for camptocormia in PD 137

differ between 3% and 17.6% [10, 13, 22, 75], and 138

large studies reported a prevalence of ca. 10% [76]. 139

As camptocormia is frequently observed in advanced 140

PD, the mean disease duration of the observed 141

patients influences the prevalence rate found in the 142

studies [77, 78]. 143

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Table 1Muscle diseases that may present with camptocormia

Dystrophies: Facio-scapulo-humeral muscular dystrophy (FSHD) [34, 36–41]Limb girdle dystrophies: Calpainopathy [42]Myotonic dystrophies: DM1 [43, 44], DM2 [45, 46]Duchenne muscular dystrophy [47]

Structural myopathies: Ryanodine receptor (RYR1)-defect [48]Four and a half LIM domain (FHL1)-mutation [49]Myofibrillar myopathy [50]Nemaline myopathy /late onset [51]Congenital myopathy [52]

Metabolic myopathies: Mitochondriopathies [52–54]Hypothyroidism [55]

Varia: Radiation-induced myopathy [56–58]Amyloidosis [52, 59, 60]

Inflammation/autoimmune: Polymyositis [52, 61, 62]Dermatomyositis [52]Inclusion body myositis (IBM) [52, 63, 64]Unspecific focal myositis [7, 65–69]Paraneoplastic myositis [70]Chronic inflammatory polyneuropathy [71]Myasthenia gravis [72–74]

Besides PD, camptocormia also occurs in other144

�-synuclein aggregation disorders, such as multi-145

system atrophy (MSA) [79, 80] and dementia with146

Lewy bodies [81]. Camptocormia is also observed in147

amyotrophic lateral sclerosis. Paraspinal muscles are148

involved quite frequently in ALS [82], and campto-149

cormia may occur, especially in patients in whom the150

onset of ALS was in the respiratory muscles [83–85].151

With regard to other neurodegenerative diseases,152

there have been individual reports of camptocormia153

in Alzheimer’s disease [86]. Focal lenticular lesions154

have also been associated with camptocormia [87].155

Patients with dystonia and involvement of axial156

muscles are another group in which camptocormia is157

common. DYT 1 mutations have been described in158

individual patients [88]. Camptocormia can occur in159

isolated as well as in combined dystonia [34, 89] and160

some authors categorize camptocormia in PD as com-161

bined (formerly secondary) dystonia [90]. Recent162

work points out that hereditary muscle diseases are163

not infrequently misdiagnosed as dystonia [34].164

Camptocormia can also be a rare pharmacolog-165

ical side effect. The substances that may induce166

camptocormia are mainly dopaminergic drugs,167

anti-psychotics, anti-epileptics and cholinesterase168

inhibitors/anti-cholinergics. The Pisa syndrome,169

which has a clinical overlap with camptocormia,170

was initially assumed to be induced by antipsychotic171

drugs. The drug list includes: L-dopa/carbidopa, L-172

dopa/benzaseride[91],L-dopa/carbidopa/entacapone173

[92], pramipexole [93], ropinirole [94], olanzapine174

[95–97], valproate [4], atomoxetine (selective nore-175

pinephrine reuptake inhibitor) [98] donepezil and 176

rivastigmine [99]. 177

Camptocormia can be a functional disorder. It can 178

develop following a blast injury [100] or as a conver- 179

sion disorder to escape anxiety-provoking situations 180

and conflicts [101, 102]. It may occur in adolescents, 181

as in a 13-year old boy with concomitant anorexic 182

behavior who refused to accept the cultural change 183

associatedwith immigration[103].Whenpsychother- 184

apy isable touncover thepurposesof thesymptom, the 185

symptoms may no longer serve any purpose, and the 186

camptocormia may disappear [101]. 187

DIAGNOSIS OF CAMPTOCORMIA 188

Clinical examination 189

The main diagnostic approach is to search for 190

the etiology. The clinical examination should focus 191

primarily on signs of myopathies and movement 192

disorders. Beside typical aspects of a Parkinson 193

syndrome this includes a search for indicators of 194

dystonia, such as sensory tricks (e.g. in these cases 195

backward walking, pressing on the thighs, stepping 196

with one foot on a chair, carrying a back pack) or 197

painful contractions of the abdominal muscles while 198

standing with a feeling of being pulled forward. 199

In contrast, in camptocormia associated with PD a 200

hardening of the lumbar paravertebral muscles can 201

regularly be palpated. These patients sometimes hold 202

their arms in a backward position to stabilize their 203

body position (back-swept wing sign). In the absence 204

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of a movement disorder, a careful search for a pare-205

sis somewhere else is important, and the pattern of206

extra-axial paretic muscles could be the key to the207

diagnosis. In myositis there could be asymmetrical208

painful paravertebral muscles with erythema and ele-209

vated temperature.210

The neurological examination should describe the211

extent of the forward bending, record the individual212

peculiarities of the posture (e.g. additional laterode-213

viation or other axial disorders) and verify that the214

bending is not fixed. At present, there is no generally215

accepted method for assessing the angle. Assessment216

of the angle is not trivial because the presentation217

may change [104]. We suggest measuring the bend-218

ing angle after having had the patient stand free for219

3 minutes. Photographs or videos can be very useful220

for this purpose.221

The course and duration of the camptocormia may222

give a hint as to its etiology. While inflammatory223

camptocormia usually shows a more rapid course224

over weeks to months, there are basically two patterns225

of camptocormia in PD: A more rapid one and one226

with symptoms worsening even after more than one227

year [8, 11, 12, 22, 105]. Afterwards, symptoms may228

remain on a plateau in some patients, while others229

might experience a second acceleration of symptoms230

later on. A more stepwise and slow progression of231

camptocormia could indicate a primary myopathic232

process. A slight to moderate CK elevation is not233

conclusive for myositis but is also seen in PD camp-234

tocormia [11, 17].235

In documenting the disease severity, it is helpful to236

record the need for technical support (like orthoses237

and walking aids), the main individual complaints238

due to camptocormia, the severity of pain, if present,239

on a numeric pain rating scale (0–10) as well as its240

frequency and localization, and the subjective burden241

of camptocormia on a Likert scale. Aspects such as242

back disorders in the medical history and the current243

and former medication (side effects, neuroleptics) are244

of interest as are the family history.245

In the literature, camptocormia in PD is much246

more accurately described than in camptocormia247

of other etiologies. Frequently, only the forward248

bending aspect is reported, the existence of pain is249

occasionally noted but further details are lacking.250

EMG251

EMG is a helpful diagnostic tool in camptocormia.252

With it, one can identify myopathic, myositic or253

neurogenic changes. The choice of muscles to be254

examined should be determined by the neurological 255

examination. These might comprise dorsal and ven- 256

tral trunk muscles (mainly paravertebral and rectus 257

abdominis muscles) in patients with movement disor- 258

ders. Performing EMG in muscles of the abdominal 259

wallcanbechallenging,especiallywith thepatient ina 260

standing position, which is necessary when searching 261

for dystonic EMG-activity. When myopathy is sus- 262

pected a distal and proximal limb muscle should be 263

added. While the EMG of the paravertebral muscles 264

can show spontaneous activity in a relaxed patient, the 265

assessment of neurogenic and motor unit pattern may 266

be more difficult, as the patients have to partially acti- 267

vate the paravertebrals. In older patients, neurogenic 268

pattern and spontaneous activity are not obligatory 269

pathological [106, 107]. Motor units of the paraver- 270

tebral muscles differ from limb muscles in that they 271

have a smaller amplitude and a shorter duration [108]. 272

Muscle imaging 273

Muscle MRI is an important diagnostic tool in 274

camptocormia as it shows typical muscle abnormali- 275

ties and the extent of the muscle affection. In addition, 276

imaging is necessary to exclude orthopedic diseases. 277

It is essential to use special MRI sequences that 278

show acute and chronic processes. Acute changes in 279

the muscle can be identified using contrast-enhanced 280

MRI sequences or the short tau inversion recovery 281

(STIR) sequence. The STIR sequence is sensitive for 282

edema and is suppressing fat tissue. However, the 283

findings are unspecific and pathological STIR find- 284

ings can be seen e.g. in myositis, trauma, denervation 285

and a wide range of muscle diseases [109–115]. 286

Ideally, the STIR sequence is combined with a 287

T1 sequence that best covers the chronic changes of 288

camptocormia: These are atrophy, often asymmetri- 289

cal, and fatty degeneration shown by hyperintense 290

signals in T1. The frequently used T2 sequence is not 291

a substitute for the T1 sequence because hyperintensi- 292

ties in T2 can resemble both edema and fat and cannot 293

support the classification of camptocormia into acute 294

or chronic stages. 295

In PD camptocormia the spectrum of muscle MRI 296

findings ranges from swelling and edema of the par- 297

avertebral and the quadratus lumborum muscles [65] 298

to findings primarily described as atrophy and fatty 299

degeneration [9, 13, 20, 22]. Previously, we suggested 300

that the duration of camptocormia in PD corresponds 301

with radiological muscle findings [116]. Edema and 302

swelling in the paravertebral, quadratus lumborum 303

and psoas muscles as acute changes were found in 304

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camptocormia duration of up to 31 months. Swelling305

as a hallmark of severe edema was only found in the306

camptocormia patients and not in the matched PD307

control group. The occurrence of fatty degeneration308

in the paravertebral muscles characterized a chronic309

phase and was found in camptocormia duration of310

37 months and longer. This model of categorizing311

can also be possibly found in camptocormia of other312

etiologies [7, 61, 65] as shown in Table 2. A disad-313

vantage of the muscle MRI is the lack of specificity.314

In particular, if muscle MRI shows exclusively acute315

changes, a muscle biopsy is indicated, because STIR316

hyperintensities cannot prove myositis. The muscle317

MRI can be used to determine the most appropriate318

biopsy site [117].319

Muscle biopsy: Methodological aspects320

Selection of biopsy site321

The most frequent indication for a muscle biopsy322

in camptocormia is to identify or exclude myositis323

involving paraspinal muscles. The biopsy site should324

be a muscle that is involved in the disease but does not325

yet show end-stage changes only. In camptocormia,326

the biopsy of a paraspinal muscle cannot be replaced327

by a limb muscle biopsy. Inflammatory diseases can328

show a very focal involvement even within a sin-329

gle muscle and can easily be missed. The clinical330

examinations and imaging by MRI or ultrasound may331

be helpful in identifying the best biopsy site. Prior332

EMG investigations exclude the muscle from biopsy,333

because needle tracks may mimic inflammatory334

processes.335

The histology of paraspinal muscles differs from336

that of limb muscles337

When comparing paraspinal muscles of elderly338

patients with their limb muscles, a higher number of339

ragged red fibers is seen in paraspinal muscles [118,340

119]. Incidental focal chronic endomysial inflam-341

mation has been reported for paraspinal necropsy342

muscles [120]. From these investigations of control343

patients, we conclude that some ragged-red fibers,344

rimmed vacuoles, COX-deficient fibers and sparse345

infiltrates of lymphocytes may be found randomly346

in paraspinal muscles and are not necessarily patho-347

logical [118].348

Myopathological findings in camptocormia349

In inflammatory diseases associated with campto-350

cormia, the myopathological findings in paraspinal351

muscles are the same as in other muscles involved 352

in these diseases. In myopathies that present as axial 353

myopathy, histology of paraspinal muscles may show 354

pathology even if limb muscle biopsies were normal 355

[121] but the experience with paraspinal muscle biop- 356

sies in these diseases is limited [122]. The spectrum 357

of diseases that should be considered is listed in Fig. 1 358

and Table 1. 359

Camptocormia in PD, however, shows a specific 360

and consistent lesion pattern as was recently shown 361

[118]. It is composed of myopathic changes with 362

type-1 fiber hypertrophy, loss of type-2 fibers, loss 363

of oxidative enzyme activity and a fine granular acid 364

phosphatase reactivity of lesions. Ultrastructurally, 365

myofibrillar disorganization and Z-band streaming up 366

to electron-dense patches/plaques were seen in the 367

lesions. Endomyseal fibrosis and fatty degeneration 368

were observed to a variable extent and seem to corre- 369

late with the duration of camptocormia [118]. In prin- 370

ciple, these changes have been described in some case 371

series before [12, 20, 123], but without the knowledge 372

of the physiological spectrum of paraspinal muscle 373

morphology, the interpretation was inconsistent. 374

PATHOPHYSIOLOGICAL CONCEPTS 375

The pathophysiological concepts for campto- 376

cormia are as heterogenous as the causes of 377

the syndrome. Primary muscle diseases, secondary 378

myopathies, inflammation and dystonia seem to be 379

the main associated diseases in camptocormia, and 380

different concepts must be assumed for each group. 381

Diseases may directly involve paraspinal muscles, as 382

with inflammatory diseases, specific muscle diseases 383

such as FSHD, limb-girdle muscular dystrophies 384

(LGMD), myotonia and metabolic myopathies. In 385

these diseases, camptocormia seem to be associated 386

with a loss of function of paravertebral muscles. 387

Fibrosis may be the reason for radiation-induced 388

myopathies [58]. 389

Some neurodegenerative diseases may cause sec- 390

ondary myopathy. In ALS the mechanism leading to 391

camptocormia is obviously the degeneration of the 392

secondary or primary motor neurons of the respective 393

muscles. In PD the pathophysiological mechanism of 394

camptocormia is not as apparent. Frequently, camp- 395

tocormia in PD was interpreted as dystonia [90] but 396

several clinical aspects (EMG results, negative sen- 397

sory trick testing, lack of positive effects of botulinum 398

toxin treatment) as well as the myopathological lesion 399

profile in biopsies argues against this assumption. 400

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Table 2Treatment of inflammatory camptocormia

Study Diagnosis n Treatment Effect on Campto-cormia Findings in thecampto-cormia duration/existence of pain paravertebral muscles

Wunderlich et al., 2002 [65] focal myositis, PD 1 methylpredniso-lone i.v.and oral

marked improve-ment 2 months (also pain) EMG: spontaneousactivity, myopathic

MRI: severe unilateraledema

Charpentier et al., 2005 [66] focal myositis, PD 1 IVIg, prednisolone i.v. partial improve-ment 21 months (also pain) EMG: myositicMRI: unilateral

accentuated edemaDiederich et al., 2006 [7] focal myositis, MSA 2 only in one case:

methylpredniso-lonei.v.

good response 1 year EMG: myositicMRI: bilateral focal

edemaDominick et al., 2006 [67] focal myositis 1 IVIg very good response 1 year EMG: myositicDelcey et al., 2002 [52] poly- and

dermatomyositis4 methylpredniso-lone i.v.

and oral, IVIg,cyclosporine

3 improved n.r. (back pain: n = 4) EMG: myositicMRI: in 3 pat. fatty

atrophic changes, in 1acute changes

Kuo et al., 2009 [62] poly-myositis 1 methylprednisolone i.v. modest improve-ment 1.5 years back painMRI: diffuse atrophy with

fatty replacementMattar et al., 2013 [61] poly-myositis 1 oral predniso-lone,

azathioprine,methotrexate,cyclosporine

none for several years MRI: total fattyreplacement

Rojana-Udomsart et al., 2010 [68] myositis associatedwith scleroderma

2 in one case prednisolone,methotrexate,azathioprine

none n.r. EMG: in one casespontaneous activity

CT: severe fatty atrophyZenone et al., 2013 [69] polymyositis/systemic

sclerosis overlapmyositis

1 oral prednisolone,methotrexate, IVIg

modest improve-ment 3 months (also pain) EMG (limbs): myogenicSpine MRI: normal

Hund et al., 1995 [164] inclusion bodymyositis

1 dexametha-sone oral mild & transient 4 years EMG:neurogenic-myopathicpattern

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Goodman et al., 2012 [63] inclusion bodymyositis

1 n.r. n.r. 18 months EMG: axial myopathyMRI: atrophy and fatty

replacementMa et al., 2013 [64] inclusion body

myositis2 n.r. n.r. 18 years, respectively 7

yearsEMG:

myopathic-neurogenicpattern, respectivelymyopathic

MRI: no structuralabnormalities in onecase; n.r. in the othercase

Terashima et al., 2009 [71] CIDP 1 IVIg markedly reduction 6 months EMG (during follow-up):chronic neurogenic,spontaneous activity

MRI (during follow-up):No abnormal signals

Kataoka et al., 2012 [73] myasthenia gravis 1 i.v. edrophonium, oralprednisolone

markedly improved 14 months EMG: no myopathyMRI: mild atrophy

Devic et al., 2013 [72] myasthenia gravis 1 oral pyridostigmine, i.v.edrophonium, IVIg,mycophenolate mofetil

none n.r. EMG: no myopathy, nospontaneous activity

MRI: severe atrophy withmajor fatty replacement

Abboud & Sivaraman, 2015 [74] myasthenia gravis 1 without effect: oralpyridostigmine, oralsteroids; with effect:IVIg plus oral steroids

significantly improve-ment 5 weeks MRI: scoliosis, nothingelse reported

Abbreviations: CIDP = chronic inflammatory demyelinating polyradiculoneuropathy; i.v. = intravenous; IVIg = intravenous immunoglobulins; MSA = multiple-system atrophy; n.r. = not reported;PD = Parkinson’s disease.

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Fig. 1. Different disease principles can cause camptocormia, and camptocormia may be symptom of a variety of diseases. The graph doesnot show the diseases in proportion to their occurrence. Abbreviations: ALS = amyotrophic lateral sclerosis; CIDP = chronic inflamma-tory demyelinating polyradiculoneuropathy; dermatomyos. = dermatomyositis; DLB = dementia with Lewy bodies; FHL1 = four and a halfLIM domain 1 gene; IBM = inclusion body myositis; MSA = multiple-system atrophy; NMJ = neuromuscular junction; periph. = peripheral;polysyn. = polysynaptic; striat. = striatal.

Explanation of camptocormia in PD by a401

proprioceptive dysregulation402

The pathophysiology of camptocormia is a mat-403

ter of debate. The lesion patterns that were seen in404

biopsies of paraspinal muscles in camptocormia give405

a first hint on the pathophysiological mechanisms406

[118]. The myopathological lesions of paraspinal407

muscles in camptocormia show remarkable simi-408

larities to lesions found in the soleus muscle after409

experimental tenotomy of the Achilles tenodon [124].410

The lesions in experimental tenotomy were generated411

only when tendons were cut but the motor nerve and412

the spinal tracts remained intact. By transsecting the413

motor nerve or the spinal tracts of the polysynap- 414

tic reflex arch in addition to the tendon, the muscle 415

lesions as well as the motor unit activity of the muscle 416

are abolished. This led to the conclusion that the mus- 417

cle lesions are the consequence of a dysregulation of 418

the functionally intact polysynaptic reflex arch: After 419

tenotomy the input information from the Golgi ten- 420

don organ is “muscle tension is too low”, and the 421

consequence is a hypercontraction of the muscle, as 422

observed, for example, as “Popeye sign” after biceps 423

tendon tears [125], and result in myopathy. In camp- 424

tocormia, the same muscle lesion pattern is observed 425

[118], but the tendons seem to be intact. Clinically, 426

paraspinal muscles in camptocormia show a painful 427

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hardening like muscles after tendon tear [125]. As428

opposed to tenotomy, where the myopathological429

changes are due to a dysregulation of the polysynaptic430

reflex arch at the level of tendons, the myopatho-431

logical changes in PD-related camptocormia may be432

due to a dysregulation of proprioception at the level433

of the central nervous system. Such an impairment434

of proprioception has been described in PD patients435

[126]. This pathophysiological concept is supported436

by the observation that lenticular lesions [87] can437

cause camptocormia and that neurostimulation of the438

subthalamic nucleus can relieve PD-related campto-439

cormia [31] as it (partially) reverts the proprioceptive440

dysregulation [127]. Later in the course of campto-441

cormia, intrafascicular fibrosis and fatty replacement442

of muscle fibers occur as secondary changes [118]. In443

this stage, camptocormia cannot be treated by proce-444

dures that act on muscle fibers. Consequently, in this445

state neurostimulation of the subthalamic nucleus has446

no effect on the bending angle [31].447

Pathophysiology of camptocormia in dystonia448

and as side effect of medication449

In isolated and combined dystonia, camptocormia450

can be addressed as an imbalance in the activity of451

agonistic and antagonistic muscles, which may be the452

reason for camptocormia as a side effect of drugs.453

Most of these drugs interfere with neurotransmitters454

such as L-dopa. Among these are dopamine agonists,455

anticholinergics, anti-psychotics, and anti-epileptics.456

TREATMENT OPTIONS FOR457

CAMPTOCORMIA458

Treatment of camptocormia depends mainly on the459

etiology and may therefore be difficult. At present460

there is an unfortunate lack of controlled studies for461

many of the different etiologies. Figure 2 illustrates a462

proposed work-up and therapy algorithm for common463

etiologies and diseases with which camptocormia can464

occur.465

Treatment of PD-associated camptocormia466

Drug therapy467

In the majority of patients, treatment with L-dopa468

gives only minimal or no improvement of campto-469

cormia in PD [6, 8, 19]. The two exceptions are470

the rare cases of L-dopa responsive camptocormia,471

possibly an off-dystonia [128], and camptocormia in472

patients with end of dose fluctuations.473

Optimizing the PD therapy may improve camp- 474

tocormia as was described with continuous subcuta- 475

neous infusions of apomorphine in a case series of five 476

PDpatientswitha follow-upofup to threeyears [129]. 477

Botulinum toxin 478

In five studies in PD patients with camptocormia, 479

botulinum toxin (BTX) was injected under EMG, 480

ultrasound or CT guidance [6, 130–133]. BTX was 481

injected into the rectus abdominis, abdominal exter- 482

nal oblique and ilio-psoas muscles either singly or as a 483

combination of several. Different types of botulinum 484

toxin A were used with different dosages per muscle 485

[134]. Of a total of 23 PD patients with campto- 486

cormia treated with BTX, four (17%) improved to 487

some extent while 19 showed no effect. In the stud- 488

ies with negative results, the injection guidance and 489

dosage were sufficient. However, several studies [6, 490

73, 130] reported that BTX injections were partially 491

successful in PD camptocormia patients with signs 492

of dystonia of the rectus abdominis muscle. 493

In conclusion, some patients with PD campto- 494

cormia may be suitable for treatment with BTX, 495

although according to the data, BTX treatment would 496

not be effective in the vast majority of them. 497

Lidocaine 498

Lidocaine was used in two non-blinded, open-label 499

studies [135, 136]. In these studies the authors defined 500

an upper and a lower subtype of PD camptocormia. 501

They performed repeated injections of lidocaine into 502

the external oblique muscle for upper camptocormia 503

and into the psoas major muscle for lower camp- 504

tocormia. The average improvement of the bending 505

angle was approximately 12◦. However, almost none 506

of the patients showed a bending angle below 30◦507

after treatment. Treatment with lidocaine shows only 508

limited improvement, so far, but further investigation 509

is needed [137]. 510

Trans-spinal magnetic stimulation (TSMS) 511

Arii et al. compared repetitive TSMS with sham 512

stimulation in PD patients with camptocormia in a 513

randomized, crossover study [138]. In the standing 514

position the angle improved immediately after the 515

stimulation by a mean of 10.9◦ and in the sitting posi- 516

tion by 8.1◦ while there were no significant changes in 517

the sham group. The observed effects remain ambigu- 518

ous as they are too limited to be clinically relevant and 519

a proposed influence of the stimulation on ascending 520

and descending pathways in the spine is conceivable 521

but were not proven [139]. 522

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Fig. 2. Proposal for a work-up and treatment algorithm for camptocormia. Abbreviations: DBS = deep brain stimulation; GPI = globuspallidus internus; iPD = idiopathic Parkinson’s syndrome; STN = subthalamic nucleus.

Deep brain stimulation (DBS)523

Although bilateral neurostimulation of the sub-524

thalamic nuclei has been shown to improve core525

symptoms of PD [140], the effect on PD-associated526

camptocormia is heterogeneous. Of about 80 studied527

patients, only about 60% showed improvement [16,528

31, 141]. Multifactorial analysis showed a correlation529

between an improvement of the bending angle and the530

time between onset of camptocormia and start of neu-531

rostimulation [31]. All patients with camptocormia of532

up to 1.5 years duration showed a beneficial effect,533

while patients with camptocormia persisting between534

1.5 and ca. 3 years showed mixed results. No patient535

with a duration of more than 40 months showed any536

improvement except for a single patient whose camp-537

tocormia was L-dopa-responsive. The bending angle538

was not a prognostic factor. Similar results were seen539

in an independent study [16].540

Surgical treatment of PD camptocormia541

Each of the so far reported 10 PD patients who542

were treated with spinal surgery due to camptocormia543

[142–146] had acute or delayed complications of var-544

ious degrees after surgical intervention. Regularly545

these patients had at least one revision [147]. The high546

revision rate may more likely to be connected with547

the diagnosis of PD than camptocormia as Babat et 548

al. [148] reported for PD patients with spine surgery 549

to various reasons other than camptocormia also a 550

revision rate of 86%. A possible explanation might 551

be the susceptibility of PD patients for osteoporosis 552

[142, 146, 148, 149]. PD patients are a high-risk pop- 553

ulation in adult spinal surgery [150]. Surgical spine 554

procedures increases the risk of a later formation of 555

camptocormia [17] and minor surgical interventions 556

in PD patients can lead to instability of the spine 557

[146]. Specifically in PD camptocormia an imminent 558

limitation is the adjacent segment instability after sur- 559

gical correction of camptocormia leading again to an 560

abnormal posture. However, in 10 surgically treated 561

PD camptocormia patients 5 reported even in the face 562

of relevant complications and a prolonged postoper- 563

ative course for recovery a benefit in their posture 564

and a reduction in back pain, 3 had an unfavorable 565

outcome and in 2 cases it was not reported. 566

Treatment of dystonic camptocormia 567

Drug therapy 568

There are some case reports of patients with 569

dopamine-responsive dystonia presenting with camp- 570

tocormia who benefitted greatly from long-term 571

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N.G. Margraf et al. / Pathophysiology and Treatment of Camptocormia 11

L-dopa therapy in low [151, 152] or sometimes high572

doses [88]. In an earlier case series of patients with573

adult-onset axial dystonia a third of these patients574

improvedunder treatmentwitheitheracombinationof575

tetrabenazine, pimozide, and an anticholinergic drug,576

or with high dose anticholinergic drugs alone [153].577

Botulinum toxin578

Overall the effects of BTX in patients with dys-579

tonic camptocormia are more homogenous than in580

those with PD-associated camptocormia. However,581

experience is still limited by small datasets and the582

lack of controlled studies. Beneficial effects have583

been reported in patients with segmental or abdom-584

inal dystonia with dystonic findings in the EMG585

after treatment with BTX injections in the upper586

abdominal muscles or the rectus abdominis [89, 154].587

However, BTX injections in abdominal dystonia were588

ineffective in two cases [6], or had only partial effects589

[155].590

Deep brain stimulation591

To date, 17 dystonic camptocormia patients were592

reported to have been treated by deep brain stimula-593

tion of the GPi [26, 27, 155–160]. Fifteen of these594

were diagnosed primary dystonia, and two probably595

had secondary dystonia. The Burke Fahn Marsden596

Dystonia Rating Scale (BFMDRS) sub-item “trunk”597

showed a reduction by 50% to 100% on the last follow598

up at between six to sixty months after DBS.599

As in other types of dystonia, a possible treat-600

ment algorithm for dystonic camptocormia would601

start with medication followed by botulinum toxin as602

secondary therapy option, and if this is unsuccessful603

by DBS of the GPi.604

Backpack treatment605

One PD patient with camptocormia who did not606

respond to BTX injections in the rectus abdominis607

muscle showed complete resolution of camptocormia608

when wearing a low-slung backpack weighting609

approximately 6 kg [161]. This benefit was prolonged610

and only ended on removal of the backpack. The611

backpack possibly stimulates a sensory trick indicat-612

ing a dystonic symptom.613

Treatment of inflammatory camptocormia614

Camptocormia in inflammatory myopathies and615

chronic inflammatory demyelinating polyradicu-616

loneuropathy can be successfully treated with617

immunosuppressive therapy but therapy response618

depends on the presence of inflammation and absence 619

of secondary changes such as atrophy and fatty degen- 620

eration. A MRI of the paravertebral muscles (e.g. T1, 621

STIR) and camptocormia duration might predict the 622

treatment outcome with good results in acute changes 623

and very limited results depending on the degree 624

of chronic muscle fatty degeneration. The choice 625

of immunosuppressive drug and its dosage should 626

be adjusted to the disease activity (cf. Tab. 2). An 627

exception is inclusion body myositis (IBM) in which 628

immunosuppressive drugs and immunoglobulins are 629

ineffective [162]. The best therapeutic approach in 630

IBM to slow progression is regular physiotherapy 631

[163]. 632

Treatment of camptocormia in primary 633

myopathies and myasthenia gravis 634

Primary myopathies and myasthenia gravis should 635

be treated according to the underlying disease. This 636

may resolve the axial syndrome as was shown for 637

riboflavin treatment of late-onset multiple acyl-CoA 638

dehydrogenase deficiency (MADD), a lipid storage 639

myopathy [165], and thyroid hormone replacement 640

therapy in hypothyroid myopathy [55]. Treatment 641

effects in myasthenia gravis are possibly favorable in 642

case of acute muscle changes and limited if chronic 643

muscles changes have already occurred (please com- 644

pare Table 2). 645

Camptocormia as side effect of several 646

medications 647

Discontinuing medications reported to induce 648

camptocormia as a side effect may improve the 649

posture. This has been shown in a study in which 650

pramipexole was discontinued in 34 PD patients after 651

which camptocormia improved [76], as well as in a 652

case report [93]. 653

Camptocormia as a dose-dependent side effect of 654

valproate monotherapy resolved within 1-2 weeks 655

after dose reduction [4]. Olanzapine-induced camp- 656

tocormia normalized within weeks to months after 657

olanzapine was discontinued [95–97]. 658

Supportive therapy independent of 659

camptocormia etiology 660

Pardessus et al. showed the efficiency of a leather 661

orthosis that straightened the patients and reduced 662

back pain [166]. About 68% wore the leather orthosis 663

at least 9 hours a day. In a prospective study, de Seze 664

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12 N.G. Margraf et al. / Pathophysiology and Treatment of Camptocormia

et al. evaluated a new orthosis based on the principle665

of thoraco-pelvic anterior distraction in campto-666

cormia combined with a physiotherapy program667

[167]. Camptocormia was significantly improved as668

shown by clinical and radiological data in a follow-up669

after 90 days. Back pain was reduced by 70%. In a670

case series with 3 PD patients with camptocormia a671

high-frame walker with forearm support was shown672

to be an effective support material [168]. Back pain673

was reduced and the patients’ ability to walk for a674

longer distance in an upright position was enhanced.675

PD patients with anterior trunk bending (UPDRS676

item posture ≥ 2) benefit from muscle stretching, pos-677

ture training and proprioceptive stimulation, as was678

shown in a randomized control study with a 2-month679

follow-up [169]. The median effects on the degree of680

bending were minimal, although statistically signif-681

icant for the treatment group but not for the control682

group.683

Orthoses, technical support material and physio-684

therapy show a relevant potential in the treatment685

of camptocormia. Considering the large number of686

chronic PD camptocormia patients with fewer thera-687

peuticoptions,morestudiesof this typearewarranted.688

Pain therapy689

Severe back pain is a frequent complaint in campto-690

cormia and is a relevant therapy target. Its importance691

is also shown by its significant correlation with the692

subjective impairment due to camptocormia in every-693

day life (Margraf et al., 2016 under review). The most694

effective treatment of this pain is to reduce the for-695

ward bending [66, 142, 143, 166, 167]. This includes696

the use of orthoses indicating that there are options697

for pain therapy even in chronic camptocormia. It698

is sometimes possible to obtain pain relief without699

any change in the posture [31]. A possible explana-700

tion could be a reduced rigidity of the paravertebral701

muscles. Classical analgetics such as non-steroidal702

anti-inflammatory drugs, opioids or muscle relaxants703

frequently have only limited effects [6].704

CONFLICT OF INTEREST705

The authors have no conflict of interest to report.706

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