Clinical manifestations

Presentation and course

Isolated neck extensor myopathy. This disorder is one of the many causes of dropped head syndrome, and it typically occurs in individuals in the seventh decade or older, more commonly in women (20). In mild cases, the patient notices difficulty keeping the head erect, whereas in extreme cases, the neck extensors become so weak that the chin rests firmly against the chest wall when the patient is standing. Careful inspection shows that the head drop results from weakness that is maximal over the mid and lower cervical and the upper thoracic regions. Symptoms and signs usually develop relatively quickly, over a period of days to a few weeks, but they can progress for months. Patients may complain of dull or burning neck pain that accompanies the progressive phase. Others note difficulty walking or holding a conversation because of the inability to look ahead. The severity of horizontal gaze disorder is associated with gait speed. Dysphagia is another common complaint that probably reflects interference with the swallowing mechanism by the flexed neck posture (45). This difficulty is relieved by passive elevation of the head. There may be mild deltoid weakness (100; 108), but deltoid muscle biopsies have been unrevealing and the significance of mild proximal limb girdle weakness in elderly people is uncertain. Obvious weakness outside the paraspinal muscles should raise suspicion that a neuromuscular condition other than isolated neck extensor myopathy is present. Recovery is usually none or minimal, or it occurs after a prolonged period of time, but there was a case report where one patient recovered spontaneously after 4 months with a short trial of physical therapy that did not seem to help, and the patient had refused cervical bracing or surgical intervention (66). This was the first case report that demonstrated rapid onset and recovery of isolated neck extensor myopathy.

Primary camptocormia. This also tends to affect elderly people (95). Women are more commonly affected than men, and an affected family member (by some reports) can be identified in up to 60% of cases (56; 95). Weakness develops over 1 to 8 years and back pain is frequent (81). However, if a patient presents with new-onset back pain with acute features of camptocormia, it is recommended to be vigilant about ruling out treatable myopathic causes (49). The thoracic, lumbar, or sacral regions may be involved alone; in some cases, wide regions of the spine, including cervical muscles, are involved. Some authors believe that isolated neck extensor myopathy and primary camptocormia are variants of the same disease (71; 101). The weakness results in an inability to stand upright. This is exaggerated by activities that require back extension, such as walking up an incline or taking off a shirt when the skin is damp. There may be proximal limb weakness, more commonly in the pelvic than the scapular region (56). However, as with isolated neck extensor myopathy, a generalized phenotype should lead to consideration of some other neuromuscular disease. The clinical course is usually benign, and patients remain ambulatory with the use of a cane.

Dropped head syndrome. Dropped head syndrome is characterized by severe weakness of the cervical paraspinal muscles that results in the passively correctable chin-on-chest deformity. Suarez and Kelly first described four patients with dropped head syndrome characterized by relatively isolated neck extensor weakness (100). Electromyogram and muscle biopsy results suggested a restrictive noninflammatory myopathy predominantly affecting the cervical paraspinal muscles.

Dropped head syndrome is a relatively benign condition that may be difficult to distinguish from more ominous neuromuscular disorders presenting with severe neck extensor weakness, including myasthenia gravis, motor neuron disease, and inflammatory myopathy. Katz first described four patients with dropped head accompanied by severe neck extensor weakness in whom no specific electromyogram or muscle biopsy abnormalities were found and coined the term “isolated neck extensor myopathy” (INEM) (45). INEM is diagnosed by the exclusion of neuromuscular causes.

Although the precise etiology of dropped head syndrome remains controversial, the most favored hypothesis proposes that the deformity is caused by injury to and fatigue of the paraspinal musculature, with secondary kyphotic postural changes and an age-dependent loss of tissue elasticity. A clinical study of 67 patients with dropped head syndrome focuses on the clinical characteristics, including the prognosis (22). Although several case reports have examined the pathological findings of dropped head syndrome, these reports have mainly focused on skeletal muscle biopsy specimens of the cervical extensor tissue. To date, no large study has examined the histopathology of the cervical extensor tissue in dropped head syndrome. The study by Endo and colleagues focuses on the histopathology of the cervical paravertebral soft tissue of patients with dropped head syndrome.

Prognosis and complications

Isolated neck extensor myopathy and primary camptocormia are essentially static conditions. Rest-related improvement has been observed in a case report of isolated neck extensor myopathy (72).

Clinical vignette

Isolated neck extensor myopathy. A 77-year-old man developed insidiously progressive difficulty breathing because of congestive heart failure. As a result, he began to sleep sitting in an easy chair. Within weeks he noticed a constant dull pain in the back of his neck. A few days later he had difficulty keeping his head in the upright position. Serum levels of antibodies to the acetylcholine receptor and serum creatine kinase levels were normal. Electrodiagnostic testing a month after onset revealed normal nerve conduction and low frequency repetitive stimulation. However, needle electromyography showed myopathic appearing motor units and recruitment patterns, restricted to segments from C5 to T4, without positive sharp waves or fibrillation potentials; the high cervical and the midthoracic regions were normal. Magnetic resonance imaging of the cervical region showed no structural abnormalities of the spine itself, although fat replacement and edema-like changes were evident in the affected muscles. Muscle biopsy of the cervical paraspinal muscles revealed increased connective tissue, necrotic myofibers, split fibers, and increased internal nuclei without inflammation or vacuoles.

No medical therapy was prescribed. The patient complained of discomfort when he wore either a firm or soft cervical collar because they rubbed against his chin when he talked, ate, or turned his head. Similarly, he found several braces uncomfortable. He also tried to avoid spending time in the upright position where the head would fall forward and, once his cardiac problems were treated, he slept in a reclined position rather than seated. He improved slightly over the following year.

Primary camptocormia. For 3 years, a 49-year-old woman noted progressive anterior curvature of the spine, most evident over the lumbar region. She had mild low back pain that increased with prolonged standing. Her mother had had the same symptoms, but they had begun much later in life. Examination showed camptocormia but no definite limb weakness. Her serum creatine kinase and acetylcholine receptor antibody levels were normal. EMG showed short duration, small amplitude motor units without abnormal spontaneous activity limited to the lumbar paraspinal muscles and sparing the limbs. No decremental response to low frequency repetitive nerve stimulation was present. Spinal MRI showed increased T1 and T2 signal suggestive of fatty changes in the lumbar paraspinal muscles. An aluminum walker helped her gait. There has been no obvious change in the degree of weakness over the past 2 years.

Biological basis

Etiology and pathogenesis

The causes of isolated neck extensor myopathy and primary camptocormia are not known. It has been postulated that, in susceptible individuals, a combination of postural changes and aging may place excessive loads on the paraspinal musculature, eventually leading to the focal myopathy (45; 72). For example, the gravitational forces pulling the head downward should increase as the head begins to fall forward. As the neck muscles are stretched, they contract inefficiently, and the head moves further into a flexed posture. This vicious cycle continues until the head rests firmly against the chest. Also, similar to developing a hypercontracted biceps muscle known as a “Popeye sign” after a biceps tendon tear due to dysregulation of the reflex arch, patients with camptocormia develop painful contractions of their muscles without an actual tendon tear but due to dysregulation of proprioception at the level of the central nervous system in patients with Parkinson disease-related camptocormia (124; 17; 118; 64). The fact that patients with extrapyramidal disorders, with their related postural changes, are susceptible to paraspinal extensor myopathies supports this hypothesis (03). Others have pointed to evidence favoring a focal inflammatory myopathy (36; 09), focal mitochondrial disease (04), or a focal dystrophy (56; 95; 122) as the etiology.

For both isolated axial extensor paraspinal myopathies, muscle histology of the paraspinal muscles reveals a nonspecific myopathic process including increased connective tissue, split fibers, and numerous fibers undergoing myonecrosis. Biopsies of limb muscles are normal (45). No biochemical or genetic abnormality has been identified. Sakiyama and colleagues reported on a family with maternal inheritance of axial myopathy and encephalopathy associated with ragged-red fibers and cytochrome c oxidase-negative fibers in muscle biopsy and a novel heteroplasmic mutation (m.602C> T) in the tRNA(Phe) gene of the mitochondrial DNA (90). Lehmann and colleagues reported a case of polymerase gamma 2 (POLG2) mutation, a protein encoding replicative mtDNA polymerase, leading to primary camptocormia (59). Paraspinal muscles appear to be particularly susceptible to age-related mitochondrial respiratory chain defects. Campbell and colleagues observed an age-related increased in cytochrome oxidase deficient (respiration-deficient) myofibers in paraspinal muscle in association clonal expansion of mtDNA deletions and depletion (10). Another mutation described as causing late-onset axial hereditary myopathy is in the ryanodine receptor 1 (RYR1) gene (116; 97).

The identification of necrosis, microvessel proliferation, and atrophy in the skeletal muscle of patients with dropped head syndrome, as well as the presence of ligament degeneration and microvessel proliferation in the chronic but not acute or subacute phases, may suggest that persistent skeletal muscle damage of the cervical paravertebral region causes subsequent ligament damage in patients with dropped head syndrome (22). A patient presented with a unique phenotype of POLG mutation, with camptocormia secondary to atypical parkinsonism not preceded by SANDO or progressive external ophthalmoplegia; such a presentation has rarely been described in the literature (91). POLG mutations should be considered in the differential diagnosis of atypical parkinsonism, even in patients without ophthalmoparesis or polyneuropathy.

Of note, iNPH and Parkinson disease both feature striatal involvement. In certain patients with these diseases, dysfunction of the striatum could particularly affect the reticulospinal pathway and lead to an imbalanced axial motor drive, which may be excessive (dystonic) for ventral muscles (eg, abdominal wall muscles) and decreased for dorsal muscles (eg, paravertebral muscles). In such cases, the chronic hypoactivation of trunk extensor muscles might result in disuse muscle atrophy. Alternatively, a compensatory hyperactivation of paravertebral muscles may counteract the excessive trunk flexion, leading to overuse myopathy over time. From this perspective, an axial dystonia can occur early, causing prolonged mechanical stress and secondary chronic myopathy of paravertebral muscles. However, this hypothesis remains speculative as dystonic patterns were not found at EMG investigation, and previous electrophysiological findings were not available, in the study by Todisco and colleagues (106).

Filamin C, encoded by the FLNC gene, is an emerging cause of cardiac or skeletal myopathies. Previous studies demonstrated the effect of FLNC splice-site mutations on sarcomere structures. However, these mutations phenotypically presented as isolated cases of cardiomyopathy. One patient’s co-occurring skeletal and cardiac myopathy, possible familial involvement, and genomic evidence supports a novel intronic FLNC splice-site mutation mechanism (38).

Although the effect of the FLNC mutation is uncertain (c. 1210+3A> G), the substitution of A with a G3 nucleotide after exon 7 in the intronic region of the ROD1 domain has been shown to disrupt RNA splicing. This can result in a loss-of-function truncated splice variant that predisposes patients to dilated cardiomyopathy. In a study, splice variants in the ROD1 domain were associated with proximal myopathies, although camptocormia had not previously been described (38). It remains unclear if camptocormia is a phenotypic presentation of the FLNC variant or if it is due to another etiology. Clinical, laboratory, and genetic testing have ruled out other causes of camptocormia.

Epidemiology

The incidence and prevalence of these disorders are not known. Isolated neck extensor myopathy occurs more commonly than primary camptocormia. Both conditions tend to come to medical attention when the onset is rapid or the degree of involvement is particularly severe. However, abnormal posture is common in elderly people, and we suspect this is attributable to axial extensor muscle weakness in at least some individuals.

Prevention

Risk factors include any condition that affects the posture (aging, Parkinson disease), activities that cause the individual to remain upright for excessive periods (sleeping in a chair), or diseases that weaken the paraspinal muscles (neuromuscular conditions, radiculopathy). Why a severe degree of weakness occurs in some individuals but not others is unknown. There are no obvious strategies for prevention.

Differential diagnosis

Axial paraspinal extensor myopathies may occur in a wide range of myopathic, neuromuscular junction, motor neuron, and neuropathic disorders or in Parkinson disease.

Table 1 gives an overview on the ever-growing number of myopathies potentially manifesting or even presenting with camptocormia.

Table 1. Paraspinal Weakness in Myopathic, Neuromuscular Junction, Motor Neuron, and Neuropathic Disorders

Myasthenia. Myasthenia gravis may affect extensor neck muscles along with ocular, bulbar, or limb muscles and is one of the more common causes of dropped head syndrome (45) or camptocormia (44). Although the dropped head sign as the first or only manifestation of the disease is unusual, a series of six patients who presented with dropped head that responded to intravenous edrophonium were confirmed to have myasthenia gravis (12; 92). A case series of five patients with myasthenia gravis were found to have concomitant paraspinous myopathy, which was less responsive to immunosuppressive therapy, indicating they may have had primary paraspinous myopathy as opposed to being secondary to the neuromuscular dysfunction (86).

Myositis. A few cases of dropped head or bent spine syndrome have been attributed to focal myositis of the paraspinal musculature, as shown by MRI and muscle biopsy. One study found that splenius capitis had the highest diagnostic yield for a muscle biopsy in diagnosing dropped head syndrome (01). Immunosuppressive treatment or intravenous immunoglobulins were effective in some of these cases (43; 123).

Muscle dystrophy. Dropped head syndrome may also be the dominant feature of a congenital muscular dystrophy, as reported in patients with mutations in the lamin A/C and selenoprotein N genes (16).

Motor neuron disease. Motor neuron diseases, including amyotrophic lateral sclerosis, may also cause neck or trunk weakness with about 1% of cases presenting this way (117; 110; 35). Specific neuromuscular disorders can be recognized by subtle findings on examination, laboratory abnormalities, or histological changes that are not characteristic of isolated neck extensor myopathy or primary camptocormia (114).

When paraspinal muscle weakness occurs as part of a generalized neuromuscular disorder, it is usually the result of the same underlying pathophysiology that causes weakness in other muscle groups. However, there may be exceptions. For example, Katz and colleagues described a patient with myasthenia gravis who continued to have persistent neck extensor weakness even after limb, ocular, and bulbar weakness responded to immune suppression therapy (45). Electromyography showed myopathic changes limited to the neck extensors, and we speculated that the head drop was initially caused by the myasthenia, but ultimately the combination of weakness and postural changes resulted in a secondary myopathy of the cervical paraspinal muscles (45). This observation was corroborated in another report (85). It is suggested to consider paraspinous myopathy early on in patients with myasthenia gravis and camptocormia who are not responding to immunosuppressive therapy to prevent unnecessary medication side effects (86). Multilevel nerve root impingement is another gray area that has been postulated as a cause for severe lumbar paraspinal weakness (77). However, others speculate that nerve root involvement alone cannot easily cause postural changes, and that paraspinal muscles affected by radiculopathy may ultimately become susceptible to myopathic abnormalities (108). The same type of hypothesis may help explain the relatively common occurrence of isolated neck extensor myopathy and camptocormia in patients with extrapyramidal disorders (73; 113; 18; 03; 57; 79).

Structural abnormalities of the spine should also be considered in patients presenting with a bent spine (21). These are easily excluded if the patient can fully extend the back while supine. Noteworthy, the dropped head syndrome may secondarily lead to cervical spine kyphosis and cervical myelopathy requiring surgery (69; 20). Radiation-induced isolated neck extensor myopathy was described in a few small studies, with the largest study including 18 patients (39). There are also reports of radiation-induced camptocormia in three studies, each describing one patient (78; 47; 94).

Drug-induced camptocormia has been reported with valproate (50), olanzapine (84), pramipexole (70), and atomoxetine, which is a selective norepinephrine reuptake inhibitor (08).

Diagnostic workup

The etiology of INEM and idiopathic camptocormia is unknown; therefore, an extensive work-up is often required to rule out mimics (Table 2). Serum creatine kinase levels are normal in the axial paraspinal extensor myopathies. Tests for acetylcholine receptor antibodies are important to exclude myasthenia gravis. Electromyography reveals myopathic changes limited to the affected paraspinal region and dystonic changes in the abdominal muscles while patients are standing. Magnetic resonance imaging may be helpful in either ruling out structural abnormalities of the spine, in demonstrating abnormal signal in damaged paraspinal muscles (56; 45), or in measuring cross sectional areas of the paraspinal muscles, which may be helpful in predicting a positive outcome in deep brain stimulation in Parkinson disease patients with camptocormia (88). Muscle biopsy of paraspinal muscles may show abnormalities specific to the many possible neuromuscular etiologies listed above; however, if myasthenia gravis, amyotrophic lateral sclerosis, and parkinsonism are excluded, a study by Chanson and colleagues suggests that a muscle biopsy should be systematically performed, as an underlying myopathy was identified in 35% of 20 patients with isolated camptocormia (14). However, histology has to be interpreted with caution because the paraspinal muscles show a variety of neuromuscular abnormalities, eg, increased fiber size variability, endomysial fibrosis, adipose tissue, and mitochondrial changes such as ragged red fibers, even in healthy subjects (125).

Table 2. Investigations to Consider in Axial Paraspinal Extensor Myopathies

Management

There are no established effective therapies for patients with primary camptocormia and isolated neck extensor myopathy. Also, the mainstay treatment would be to treat the underlying etiology, which is not always evident. Cervical collars or neck braces, along with physical therapy, may be the most practical supportive treatment options. However, it is difficult to find a suitable collar that can support the neck and yet be comfortable. Patients find that soft or hard cervical collars rub against the chin, interfering with speech and rotation of the neck. The best approach Katz and colleagues found is to prevent forward bending by supporting the head with a brace, which is connected to a firm padded support that rests against the chest wall (45). It has an open, lightweight design that provides some flexibility and reduces heat retention. Alternatively, patients have used a custom brace that supports the head from behind, using a rigid backboard attached to a harness worn around the trunk. Both collars require referral to an orthotic specialist. Surgical approaches help with the cosmetic and physical challenges but restrict the range of neck motion and present inherent risks of surgery in the elder patient population. However, higher success rates were found with cervicothoracic arthrodesis approached with combined anterior and posterior fusion early in the disease course (13). A study investigating the surgical strategies and outcomes of dropped head syndrome demonstrated better clinical outcomes in patients with T1 slope smaller than C2-C7 cervical angle, regardless of the extent of fusion (67). Current research is focused on developing a neck exoskeleton incorporating multi-degree-of-freedom elastic mechanism, which allows neck movements in line with anatomical movement while ensuring neck stability (107).

Patients with camptocormia benefit from the use of a walker. This compensates for the trunk weakness by allowing the patient to use the arms for support. With either condition, we usually suggest that patients try to minimize the time spent standing or sitting with the head or trunk unsupported because there is anecdotal evidence that strict bed rest may lead to improvement.

Schroeteler and colleagues used a high-frame walker (HFW) with forearm support in three patients with parkinsonian camptocormia (93). Posture improved in all patients while standing and walking with the HFW. Walking distance in the upright position increased, and the occurrence of back pain was reduced. These authors observed sustained therapeutic effects with a HFW in a total of 20 patients and suggest a controlled study over a longer period.

Repeated injections of lidocaine into the external oblique muscle (for upper camptocormia) and into the poses major muscle (for lower camptocormia) has been reported to only partially improve the angle of bending by around 12 degrees on average, which suggests that further investigations are needed (27; 26; 28; 64).

According to Margraf and colleagues, there have been reports of medication-induced camptocormia, which may improve once the offending agent is discontinued (64). Examples of medication-induced camptocormia include pramipexole in a case report (70), pramipexole in 34 patients with Parkinson disease (120), valproate monotherapy in a dose-dependent fashion (50), olanzapine (112; 84; 34), and other antipsychotics (06), which all improved after discontinuing or reducing the offending agent.

Dystonic forms of camptocormia may respond to sensory tricks. A Parkinson disease patient with camptocormia, for example, had consistent and sustained benefit by wearing a 6-kilogram backpack (32). Botulinum toxin has also been tried in this group of patients, although the overall data suggest lack of complete benefit (64). Several case reports have described improvement with either low or high dose L-dopa therapy (111; 65; 74; 64; 68). In idiopathic and parkinsonian camptocormia, several publications advocate the use of deep brain stimulation (DBS), but they also report variability in results (89; 109; 02; 119). Marked degeneration of the paraspinal muscles may predict negative outcome (02). Sakai and colleagues conducted a retrospective study of 14 patients with Parkinson disease with camptocormia whose lumbar paraspinal muscles’ cross sectional areas and width were measured by a lumbar MRI prior to undergoing subthalamic nucleus deep brain stimulation (STN-DBS), and they found that the cross sectional areas and width were significantly larger in four patients (28.6%) who responded well to STN-DBS and were labelled as effective (88). Of the remaining patients, five (35.7%) were partially effective, and five were noneffective (35.7%), and therefore, measuring cross sectional areas of paraspinal muscles preoperatively can potentially be used as a good predictive marker regarding outcome of deep brain stimulation in patients with Parkinson disease and camptocormia. Two other studies showed that deep brain stimulation can improve Parkinson disease-associated camptocormia (60; 52; 53) and postural trunk deformities. The pooled results of these single cases and small case series warrant a randomized clinical trial of deep brain stimulation in parkinsonian camptocormia.

Corticosteroids generally have no therapeutic role if there is strong diagnostic evidence of paraspinal axial myopathy (36; 45). Note that responsiveness to corticosteroids has been described in cases that clinically correspond to isolated neck extensor myopathy, but these had histological evidence of paraspinal inflammation or high serum creatine kinase levels (09; 87). Empirical therapy with corticosteroids or pyridostigmine may be tried if there is sufficient concern that myasthenia gravis is present. One patient with isolated neck weakness was suspected of having a mitochondrial myopathy with ragged red fibers and responded to a combination of coenzyme Q and vitamins (04). Other myopathies with an axial syndrome that may resolve with treatment of the underlying etiology include treatment with riboflavin for a lipid storage myopathy known as late-onset multiple acyl-CoA dehydrogenase deficiency (MADD) and thyroxin for hypothyroid myopathy (48; 76; 64).

Surgical treatment of the spine in Parkinson disease patients with camptocormia did not show promising results overall (64; 75).

Dropped head syndrome can be classified into three groups based on preoperative radiological parameters: type 1, sagittal vertical axis ≤ 0 mm and PI-LL ≤ 10°; type 2, sagittal vertical axis > 0 mm and PI-LL ≤ 10°; and type 3, PI-LL > 10°. Several surgical strategies for dropped head syndrome have been reported, including posterior multiple-level fixation or combined anterior and posterior cervical fixation (Table 2). In two cases of dropped head syndrome, posterior cervical facetectomies with pedicle screw application were first performed, followed by multilevel anterior cervical discectomy and fusion with posterior rod/pedicle/screw fusion. In the second case, the final posterior fixation was accompanied by an additional laminoplasty.

Thirty-six consecutive patients with Parkinson disease who underwent GPi-DBS were reviewed. The total and upper camptocormia angles (TCC and UCC angles) derived from video recordings of patients who received GPi-DBS were used to compare camptocormia alterations. Correlation analysis was performed to identify factors associated with the postoperative improvements. DBS lead placement and the impact of stimulation were analyzed using Lead-DBS software. Eleven patients manifested presurgical camptocormia: seven had lower camptocormia (TCC angles ≥ 30°; TCC- camptocormia), three had upper camptocormia (UCC angles ≥ 45°; UCC- camptocormia), and one had both. Mean follow-up time was 7.3 ± 3.3 months. GPi- DBS improved TCC-camptocormia by 40.4% (angles from 39.1° ± 10.1° to 23.3° ± 8.1°, p = 0.017) and UCC-camptocormia by 22.8% (angles from 50.5° ± 2.6° to 39.0° ± 6.7°, p = 0.012). Improvement in TCC angle was positively associated with presurgical TCC angles, levodopa responsiveness of the TCC angle, and structural connectivity from the volume of tissue activated to the somatosensory cortex. Greater improvement in UCC angles was seen in patients with larger presurgical UCC angles. This study demonstrates the potential effectiveness of GPi-DBS for treating camptocormia in patients with Parkinson disease.