Deep Brain Stimulation for Camptocormia Associated with Parkinson’s Disease

Camptocormia, which is also known as bent spine syndrome, is characterized by abnormal posture of the trunk with marked forward flexion of the thoracolumbar spine, which increases during standing and walking and abates in the recumbent position (Azher & Jankovic, 2005). Camptocormia is a disabling symptom that occurs during the course of Parkinson’s disease (PD), but the optimized medical and surgical therapy for PD-associated camptocormia remains to be established (Finsterer & Strobl, 2010; Doherty et al., 2011). PD-associated camptocormia is generally thought to be unresponsive to levodopa (Azher & Jankovic, 2005). In most patients with PD, the extreme anterior bending is not or poorly improved, or even worsened, in response to levodopa administration, and the severity of the bent spine is often unchanged during the medication-on and -off phases (Melamed & Djaldetti, 2006), although an excep‐ tional case has been reported (Ho et al., 2007). Although some reports have shown that deep brain stimulation (DBS) in the subthalamic nucleus (STN) (Hellmann et al., 2006; Yamada et al., 2006; Sako et al., 2009; Umemura et al., 2010; Capelle et al., 2011; Asahi et al., 2011) and globus pallidus internus (GPi) (Micheli et al., 2005; Capelle et al., 2011; Thani et al., 2011) is effective in treating camptocormia, the overall efficacy of DBS in relieving PD-associated camptocormia has not been determined. This review introduces the use of DBS in the treatment of medically refractory camptocormia in patients with PD.


Introduction
Camptocormia, which is also known as bent spine syndrome, is characterized by abnormal posture of the trunk with marked forward flexion of the thoracolumbar spine, which increases during standing and walking and abates in the recumbent position (Azher & Jankovic, 2005). Camptocormia is a disabling symptom that occurs during the course of Parkinson's disease (PD), but the optimized medical and surgical therapy for PD-associated camptocormia remains to be established (Finsterer & Strobl, 2010;Doherty et al., 2011). PD-associated camptocormia is generally thought to be unresponsive to levodopa (Azher & Jankovic, 2005). In most patients with PD, the extreme anterior bending is not or poorly improved, or even worsened, in response to levodopa administration, and the severity of the bent spine is often unchanged during the medication-on and -off phases , although an exceptional case has been reported (Ho et al., 2007). Although some reports have shown that deep brain stimulation (DBS) in the subthalamic nucleus (STN) (

Definition and diagnosis
Camptocormia was first described by Earle (1815) and Brodie (1818). Camptocormia, which is also referred to as "bent spine syndrome", was initially considered, especially in war times, to be a psychogenic disorder and a conversion reaction to war stress (Karbowski, 1999). Camptocormia is associated with various etiologies, including parkinsonian syndromes, dystonia, vascular lenticular lesions, and muscular and rheumatologic disorders. It was first described in association with PD by Djaldetti et al. (1999).
The term camptocormia is now used to describe marked forward flexion of the thoracolumbar spine that varies between 30 and 90 degrees, presents in a sitting position and typically increases during walking, and completely disappears in the recumbent position, but there are no criteria with a clear consensus for diagnosing camptocormia. Most of the diagnoses are made by subjectively assessing the patient's posture. Diagnosing camptocormia in PD patients is based on clinical examination alone. Nevertheless, some specific findings might suggest alternative diagnoses. For example, weakness of the truncal extension suggests concomitant myopathy or anterior horn cell disease. In addition, camptocormia can occur in other parkinsonian syndromes, such as multisystem atrophy, progressive supranuclear palsy, or corticobasal degeneration. Patients with psychogenic disorders sometimes develop movement disorders due to conversion syndromes or malingering. Bent spine that is due to simple kyphosis that is associated with degenerative vertebral spinal changes is easily ruled out, as this phenomenon remains largely unchanged when the patient is in the recumbent position.

Epidemiology
Among the 16 patients with camptocormia that have been described by Azher & Jankovic 2005, the most frequent etiology is PD. The reported prevalence of camptocormia in PD varies widely. Four studies have described the prevalence rates of camptocormia in patients with PD as being between 3% and 6-17% (

Clinical features
Camptocormia occurs mostly in patients with PD in more advanced stages of disease progression, but, in a few cases, it appears even in the early stage . In some patients, the onset is subacute with the development of significant flexion over days to months (Lepoutre et al., 2006: Margraf et al., 2010Spuler et al., 2010). In the majority of patients with camptocormia, the initial symptoms of PD are bradykinesia and rigidity and, less frequently, tremor. In almost all patients, the initial signs and symptoms are predominantly asymmetrical . The truncal forward flexion is more prominent when standing (see Fig. 1A) and walking, but complete straightening of the back in the recumbent position (see Fig. 1B). Normally, the strength in the abdominal and paravertebral muscles is normal. Some patients can, upon external command or strong self-will, straighten themselves up, but only for very short periods and at the expense of severe fatigue . In quite a number of cases, camptocormia is associated with lower back pain (Bloch et al., 2006;Lepoutre et al., 2006;Margraf et al., 2010), but, in others, it is painless . Some patients report a feeling of being pulled forward or a sensation of tightening in their abdomen (Azher & Jankovic, 2005). If the deformity is long established with secondary fixed changes, patients might complain of breathlessness due to restricted lung capacity or of difficulty lying flat in bed due to hip or knee contractures; the latter can be accompanied by skin irritation in the flexed segment (Bloch et al., 2006). Neurological examination often reveals marked axial rigidity (Bloch et al., 2006;Lepoutre et al., 2006). The strength of the trunk and hip extension are normal unless testing is precluded by fixed posture or pain (Lepoutre et al., 2006). The paraspinal muscles can have a wooden consistency, and the rectus abdominis often feels tense (Azher & Jankovic, 2005). There might be compensatory hyperextension of the neck in order to obtain a normal visual field. There is often mixed deformity, with deviation also in the coronal plane.

Pathogenesis of camptocormia in PD
The pathophysiology of the axial postural abnormalities in PD is not well understood, and it seems to be heterogeneous. However, two possible causes for the camptocormia genesis in patients with PD have been proposed: dystonia and myopathy.

Dystonia
Axial or action dystonia is considered a possible etiology of camptocormia in patients with PD

Myopathy
Recent studies have shown detailed evidence for camptocormia that is caused by a myopathy of the paraspinal muscles. Gdynia  cormia with electromyography, muscle magnetic resonance imaging, and biopsy of the paravertebral muscles. They showed increased levels of creatine kinase in 9/15 patients, myogenic electromyographic changes in 8/15 patients, and myopathic changes in the muscle biopsies in 12/15 patients. They claimed that the cause of camptocormia in idiopathic PD is a focal myopathy and that the myopathy has a progressive course, resulting in degeneration of the paravertebral muscles.

Pharmacotherapy
In the majority of cases with advanced PD, camptocormia is thought to be unresponsive to levodopa (Azher & Jankovic, 2005;Margraf et al., 2010). Depending on the investigated cohort, up to 20% of the patients with PD and camptocormia profit from levodopa therapy (Bloch et al., 2006). The adjustment of dopaminergic therapy by carbidopa-levodopa and entacapone has been shown to result in improvements in camptocormia. Fujimoto (2006) has described the deterioration of camptocormia in patients who were treated with dopamine agonists, thus suggesting that the withdrawal of these agents might lead to an improvement of camptocormia in some cases. The poor responses to these medical agents can be explained by the fact that, when postural abnormalities and postural instabilities appear, patients are already at an advanced stage of the disease with severe axial symptoms, and all of their symptoms are known to respond poorly to levodopa, suggesting the involvement of non-dopaminergic pathways (Campbell et al., 2003). Furthermore, postural reactions that support surface perturbations are resistant to dopaminergic therapy (Carpenter et al., 2004).
In patients who seem to have a predominantly dystonic element, another treatment option might be botulinum toxin injections in the rectus abdominis muscles (Azher & Jankovic, 2005;Jankovic, 2009;Bonanni et al., 2007;Lenoir et al., 2010). Azher and Jankovic (2005) have found this to be successful in selected patients, but few have reproduced their positive results.

Spinal surgery
Spinal surgery has been used to attenuate postural abnormalities in patients with camptocormia associated with PD, whereas it has significant complications, and often requires revision surgery (Babat et

DBS
Stereotactic neurosurgery of the basal ganglia is a therapeutic alternative for patients with advanced PD. As DBS of the STN or GPi produces a significant improvement in the motor symptoms in patients with severe PD, it also can be effective in treating camptocormia associated with PD (see Table 1.).

GPi-DBS
The GPi is an alternative target that can be considered in the treatment of camptocormia. Previous research on patients with PD and camptocormia that was treated with GPi-DBS is limited to only four cases, with reports of no improvement in posture in one and improvement in posture in three (Micheli et

Conclusion
Reports of success in controlling axial posturing in patients with camptocormia with both STN and GPi stimulation support the notion that the basal ganglia plays an important role in the maintenance of posture. Although both STN-DBS and GPi-DBS can be potential surgical means for treating camptocormia in patients with PD, further studies need to be performed in order to confirm this conclusion and to select PD patients with medically refractory camptocormia who are optimal candidates for STN or GPi DBS.