CASE A

An 80 year old man developed head ptosis insidiously over a period of few weeks. A week before this he had an upper respiratory tract infection and also experienced transient sharp pain over the left and then the right shoulder. He had no diplopia, dysarthria, dysphagia, limb weakness, or fatiguability. Examination showed severe neck extensor weakness, Medical Research Council (MRC) grade 2. Muscle strength was normal in all other cranial, proximal, and distal limb muscles. Serum creatine kinase (CK) was 362 IU/l (normal 24–195) at presentation. Anti-acetylcholine receptor antibody was not detected. Repetitive nerve stimulation of right biceps, right nasalis and right trapezius was normal. A therapeutic trial of pyridostigmine failed. Cervical spine MRI did not show significant compression of the cord, roots, or any specific changes in the paraspinal muscles. An EMG disclosed positive sharp waves restricted to lower cervical paraspinal muscles. To reduce confounding from neuropathic changes secondary to coexistent age related spondylotic changes, the thoracic paraspinal muscle was chosen for biopsy. The pathological findings were mixed. There were neuropathic changes such as angular atrophic fibres; occasional nuclear sacs, target and targetoid fibres as well as myopathic features such as the presence of hypertrophic and split muscle fibres; a few necrotic, degenerating and regenerating fibres; increased internalised nuclei, and mild endomysial fibrosis. No type grouping was noted, but there was massive type I predominance. No specific treatment was offered. A few months later, he started to improve. At follow up 2 years later, he was able to keep his head up for prolonged periods, especially in the sitting position. However, he was more symptomatic while standing. He reported an overall 60% subjective improvement in neck strength and weakness had not progressed to other muscles.

CASE B

A 74 year old man with diabetes mellitus and hyperlipidaemia (for which he had been taking a statin for a few years) complained of progressive anterior curvature of the spine associated with proximal limb weakness for few months. On examination, he had moderately severe anterior thoracolumbar curvature that could be extended passively. Diffuse weakness was present; proximal limb strength was MRC grade 4 and distal, 4+. Electrodiagnostic evaluation only showed evidence of an axonal polyneuropathy, consistent with diabetes. Serum CK was persistently raised (367 IU/l). Spine MRI only showed mild degenerative changes. Anti-acetylcholine receptor antibody was not detected. Biopsy of the rectus femoris showed increased fibre size variability, necrosis, mild fibrosis, occasional red rimmed vacuoles, and one fibre which stained positive for ubiquitin, suggestive of inclusion body myositis. However, inflammation or amyloid deposition were not seen. Despite stopping statin, his weakness continues to progress and CK has remained raised (239 IU/L).

CASE C

A 59 year old woman presented with a 4 year history of progressive, painless anterior curvature of the spine. She had a family history of facioscapulohumeral muscular dystrophy but not of bent spine. Examination showed camptocormia along with scapular winging and mild facial and proximal weakness. Her CK was at the upper limit of normal, 186 IU/l. An EMG showed short duration, small amplitude motor units with early recruitment in the proximal muscles. Abnormal spontaneous activity was seen in the thoracic paraspinal muscles. No decremental response to repetitive nerve stimulation was present. Spine MRI was unremarkable. 4q35 gene deletion, consistent with facioscapulohumeral muscular dystrophy, was detected.

CASE D

A 63 year old woman developed slowly progressive, painless thoracolumbar stoop of about 30 degrees over 8 to 9 years. The deformity was not fixed and was worse in the standing position, better sitting, and minimal while lying down. There was no family history of similar weakness. She had been taking lipid lowering drugs for 10 years and symptoms did not improve on their withdrawal. Weakness was demonstrable in the thoracic paraspinal and proximal limb muscles. Her CK was persistently raised at 606 IU/l (after withdrawal of atorvastatin for 6 months). Anti-acetylcholine receptor antibody was not detected. Spinal MRI showed mild degenerative changes in the cervical spine and normal thoracic spine. No specific changes were seen in the paraspinal muscles. Spontaneous activity consisting of positive sharp waves, fibrillation potentials, and complex repetitive discharges were only seen in the right lower cervical paraspinal muscles. Biopsy of the rectus femoris muscle disclosed rare necrotic and regenerating fibres, mild increase in fibre size variability, internal nuclei and minimal fibre type grouping. No specific diagnosis on the type of myopathy could be made. Although she subjectively felt slightly subjectively worse at a review 9 months later there was little change to her condition.

HEAD DROP

Table 1 shows the various neuromuscular disorders reported to cause head ptosis. Myasthenia gravis, especially in elderly people²⁶ and amyotrophic lateral sclerosis are the commonest causes. The predilection of these diseases for focal or segmental onset may explain this. Severe isolated antecollis causing forced anteroflexion of the neck occurs in parkinsonian syndromes. Rivest et al have documented antecollis in four of their necropsy proved cases of multisystem atrophy (MSA).^12,13 The abnormality develops, sometimes in a subacute manner over a period of weeks, in the late or middle stages of the disease. The neck can only be passively and forcibly extended to its normal position with difficulty. None of the patients had convincing dystonic spasms of the anterior neck muscles, although deeper muscles may be involved. Speech, swallowing, and upgaze deficits are often associated. Trials of botulinum toxin into both sternocleidomastoid muscles are ineffective and response to levodopa generally disappointing.^12,13 Earlier case reports have also documented the association between MSA and head drop.^27–29

Yoshiyama et al¹⁴ published a series of seven patients with parkinsonism exhibiting head drop, four of whom carried a diagnosis of probable MSA. Although at rest there was no anterior neck spasm, attempts to extend the head voluntarily or passively was accompanied by contraction of the sternocleidomastoid muscles on surface EMG in all of these patients. There was no correlation between the severity of the head ptosis and parkinsonism. Three patients had improvement of neck symptoms with treatment of parkinsonism, whereas one worsened. A recent report described head ptosis in seven out of 459 patients evaluated for parkinsonism.¹⁵ All seven had features of MSA. Interestingly these patients were also documented to have weakness as well as electrophysiolgical and pathological features of myopathy in the neck extensor muscles. Okamiya et al reported a patient with vascular parkinsonism and neck extension weakness who had myopathic changes in the extensor muscles.³⁰ One of our patients (listed JHH case 2 in table 3), who has some clinical evidence of MSA, showed mixed myopathic and neurogenic features in the paraspinal muscles.

IDIOPATHIC HEAD DROP

In some cases, no obvious aetiology for the head drop is apparent even after extensive evaluation and on prolonged follow up.^2,31–33 Combining the data from various reports of idiopathic head ptosis in the literature and patients seen at our institution (table 3), the following profile of idiopathic head ptosis emerges. The female to male ratio is 3:2. Mean and median ages at presentation are 74.5 and 73 respectively. The onset is often subacute, over days and weeks rather than months. Two of our patients and one that was reported by Lerman³³ had a history of significant weight loss. Discomfort at the back of the neck is reported in some patients but other sensory abnormalities are not prominent. The weakness is profound in the neck extensors, and involvement of contiguous proximal muscles is at most modest. The CK was normal in all but two patients. Katz at al² reported oedema-like changes and atrophy of the neck extensor muscles on MRI. An EMG of the paraspinal muscles was remarkable for the increased reports of spontaneous activity. Fibrillations were present in nine and positive sharp waves in one out of the 15 patients for whom EMG data are available. Interestingly, such abnormalities were pronounced in the lower cervical segments; and in one case reported by Katz et al,² extended to the midthoracic region. The motor unit action potentials in most cases are described as having short duration and small amplitude with early recruitment. However, this has to be interpreted with caution as paraspinal motor unit action potentials are generally small and may have multiple turns even in normal individuals. EMG of the limb muscles is mostly unremarkable. The histology of limb muscles is normal or reveals mild non-specific myopathic changes such as increased fibre size variability. In two of our cases there is some evidence of denervation. The paraspinal muscle biopsies show less subtle but again non-specific changes such as fibrosis, increased fibre size variability, “moth eaten” fibres, and myofibrillar disarray. Degeneration, regeneration, and necrosis were reported by Jaster et al³² and also seen in one of our patients. Interestingly, as mentoned above, similar biopsy findings have been reported in the neck extensor muscles of patients with parkinsonism who also have head drop,^15,30 suggesting that these changes may not be specific for a neuromuscular disorder.

The weakness remains localised and in most cases stabilises after a short period of progression. In some patients (including our case A) there is some documented recovery. Secondary skeletal deformity can result in disability even after good recovery of neck strength,³² highlighting the importance of maintaining good neck posture during the period of weakness. Immunosuppressive agents have been tried for varying periods with disappointing results overall. Rose et al⁷ reported a positive effect with prolonged corticosteroids, but their patient had generalised weakness and inflammatory infiltrates (albeit scanty) in one biopsy. There may be a role for cervical spine fusion in allowing patients with disabling and non-recovering head drop to maintain a functionally useful head position.

Camptocormia

The causes of camptocormia are summarised in table 2. As in head drop, several neuromuscular diseases can present with segmental involvement of the postural muscles, resulting in camptocormia.

Amyotrophic lateral sclerosis (ALS)

The kyphoscoliotic posture along with head drop is typical in patients with moderately advanced ALS. Involvement of paraspinal muscles was described by Gower in his account of patients with ALS,¹⁷ “In most cases the wasting involves the muscles of the back, and it sometimes begins in them”. Our group had previously reported a patient with ALS who developed severe camptocormia, requiring him to support himself with hands on his thighs. Limb muscles were less involved in this patient.¹⁸

Myopathy

Most generalised myopathies, because of pelvic girdle weakness, cause lumbar lordosis rather than kyphosis. The exception may be inclusion body myositis (IBM), This was reported as a cause of erector spinae weakness by Hund et al.¹⁹ A 70 year old man developed back and later leg weakness over a period of months. The CK was slightly raised. An EMG showed spontaneous activity and polyphasic motor units with reduced recruitment in the paraspinal muscles. A biopsy of a relatively non-atrophic part of the paraspinal muscles was reported to show morphology typical of IBM. The predisposition for focal muscle weakness may explain the occurrence of camptocormia in IBM. Alternatively it may occur as a secondary phenomenon. The preferential weakness of the quadriceps over the iliopsoas often forces the patient to lock the knee in extension and predisposes to a bent over posture for better balance. This may stretch the back muscles excessively, putting them in a position of mechanical disadvantage and in turn lead to further bending. Katz et al has proposed an important role for mechanical factors in the evolution of head drop.² A similar pathophysiology may cause camptocormia in IBM. Nemaline myopathy involves the paravertebral muscles and can cause kyphoscoliosis or lordosis.³⁵ This congenital myopathy can rarely present in adult life. A case of a 62 year old woman with adult onset nemaline myopathy who presented with severe camptocormia has been reported.²⁰ Furthermore, nearly half the cases of adult onset nemaline myopathy in the literature have been associated with head drop.^5,6 We think that facioscapulohumeral muscular dystrophy has not been previously reported as a cause of camptocormia (case C). Interestingly in the series of Lange et al on head ptosis there was one patient with facioscapulohumeral muscular dystrophy.¹ In the series of Serratrice et al³⁶ one patient had type I predominance (in quadriceps/deltoid muscle biopsy) and fingerprint morphology on ultrastructure, suggestive of a congenital myopathy.

Extrapyramidal disorders

A mild stooped posture is a hallmark of parkinsonism, but severe anterior curvature is not common. Djaldetti et al²¹ described eight patients with presumed idiopathic Parkinson's disease, at Hoehn and Yahr stage 2 to 4, mean age of 66±5, and symptom-duration of 13.1±5.1 years who had severe forward flexion of the thoracolumbar spine. This was apparent on standing, less obvious while sitting, but disappeared in the supine position. There was no mention of the nature of onset. The EMGs of the paraspinal muscles done in five patients were normal. Three patients apparently had immediate and reversible aggravation of the bent spine with levodopa therapy whereas the others improved. The authors postulated that camptocormia in parkinson's disease may represent a type of dystonia.

Postencephalitic parkinsonism has also been reported to cause curvature of the spine. Onuaguluchi²² reported five cases in 1964, followed a year later by a series consisting of 14 cases from Martin.^23,37 The latter included seven photo illustrated case histories. The spinal curvature in these patients was in both anteroposterior as well as lateral planes and diminished in the supine position. In many patients it was noted to extend “from sacrum to neck”. In one woman the forward flexion of the neck was only seen when she was blindfolded. There was no consistent relation of the spinal curvature to the side of greater muscular rigidity. Three patients underwent stereotactic surgery. One patient received lesions to the ventrolateral thalamus and pallidum and another to the pallidum alone, ipsilateral to the concavity of the spine. A third patient received a lesion to the pallidum contralateral to the side of spinal curvature. In all the cases rigidity and tremor on the opposite side was abolished; but the spinal curvature was corrected only in the cases where the stereotactic lesion was placed ipsilateral to the concavity of the spinal curvature. Animal work by Ferrier,³⁸ Demas-Marsalet³⁹ and Hassler⁴⁰ had previously shown that unilateral caudate lesions could cause a similar deformity of the spine in animals, which can be corrected by destruction of the contralateral head of the caudate nucleus. Severe pathological changes have been described in the caudate nucleus in postencephalitic parkinsonism.⁴¹ Martin hypothesised that tonic activity in the caudate nuclei and its efferent pathways to the pallidum might play an important part in maintaining spinal posture.⁴¹

The slowly progressive and chronic forms of a rare encephalomyelitis that occurs among the Lakut people of Siberia, termed Viliuisk encephalomyelitis,²⁴ is also characterised by a forward bent posture. Other features include rigidity, bradykinesia, dementia, and dysarthria. Pathological findings include multiple areas of inflammation, necrosis, perivascular leucocytic cuffing, spongiform changes, and fibrosis as well as marked atrophy of the basal ganglia.²⁴

Camptocormia was reported as a side effect of sodium valproate toxicity in a 23 year old epileptic patient.²⁵ Interestingly the deformity resolved when the plasma valproate level dropped to about 300 μmol/l, only to return 4 months later when the plasma concentration rose to about 330–530 μmol/l. This patient had no other extrapyramidal features. Reversible parkinsonism has been well documented as a rare side effect of valproate^42,43 and an extrapyramidal mechanism might have been responsible for the effect of valproate on spinal posture.

IDIOPATHIC CAMPTOCORMIA

In some cases of camptocormia, such as head ptosis, the clinical abnormality remains confined to the back and no apparent cause is found even on prolonged follow up.^{16,36,44–47} Is idiopathic camptocormia a distinct entity? Table 4 summarises the various reports on this condition. The data from these studies were combined with our cases B and D to develop a profile of idiopathic camptocormia. The incidence of camptocormia, like head drop, increases with advancing age. All but eight patients developed it at an age older than 60. The earliest age of onset is 49 years. The female to male ratio is about 3:1. The weakness is mainly confined to the extensor muscles of the spine. Onset and progression are more chronic compared with head drop, often extending over a period of months to years. Mild back discomfort was present in a few. Sensory symptoms were absent. The presence of a family history in some patients^36,46 suggests that investigations for genetic and congenital neuromuscular conditions such as facioscapulohumeral muscular dystrophy and nemaline myopathy may result in better characterisation of the idiopathic cases. The CK is raised in cases B and D and in some of the cases described by Hilliquin et al⁴⁸ and Serratice et al. ³⁶ The paraspinal muscles have been reported to show atrophy and a heterogenous appearance on radiological examination (CT or MRI). The EMG findings are not uniform, with reports of both myogenic and neurogenic features. In case D, spontaneous activity consisting of positive sharp waves, fibrillation potentials, and complex repetitive discharges is seen only in the right lower cervical paraspinal muscles, probably an incidental finding. Ehrenstein reported complex repetitive discharges in the lumbar paraspinal and limb muscles in his single case report.⁴⁷ The paraspinal muscle biopsy findings are generally myopathic with increased fibrosis, variation in fibre size, and atrophy. Limb muscle histology is variable and no definite pattern was discernible. Cases B and D had necrotic muscle fibres, and the former rimmed vacuoles, but no specific diagnosis could be made. Information on therapeutic options is sparse and difficult to interpret.^16,47,48 Some authors have reported dramatic recovery with intravenous methylprednisolone.⁴⁸ The early use of corsets and other forms of spinal support may be useful to prevent the formation of fixed secondary deformities.

Idiopathic head ptosis and camptocormia: possible pathophysiological factors

Head ptosis and camptocormia are age related disorders

Idiopathic head ptosis and camptocormia occur mainly in those beyond the age of 60 and are almost never seen at ages less than 50 years. It seems that the age at presentation of head ptosis and camptocormia is advanced even in patients with an underlying disorder. In a recent study of 10 elderly patients with myasthenia gravis, age range 80–88 years, head drop was the commonest presentation, occurring in six patients.²⁶ By contrast, ptosis was the presenting complaint in only three patients.²⁶ Nemaline myopathy in childhood is associated with spinal abnormalities such as rigidity, scoliosis, and lumbar lordosis. However, in adult onset cases campocormia²⁰ and a high incidence of head ptosis^5,6 have been reported.

Katz et al² have proposed that in elderly people, age related loss of tissue elasticity and mild kyphosis⁵⁰ predisposes to chronic stretch injury of paraspinal muscles and may contribute to the development of head ptosis. Similar factors may be involved in the pathogenesis of idiopathic camptocormia. As discussed above, some of the reported histological changes in the paraspinal muscles of patients with idiopathic head ptosis were also seen in those with an obvious extrapyramidal cause,^15,30 suggesting that these changes may be non-specific changes, resulting from chronic mechanical strain rather than a specific myopathic disorder. Furthermore, in a study comparing the cervical paraspinal muscle morphology in patients with cervical myelopathies and normal necropsy controls, necrosis, core-targetoid changes, type II atrophy, and type I predominance were seen in both groups with similar prevalence and severity.⁵¹ The pathological abnormalities were more common and severe with increasing age of patients in disease and control biopsies.⁵¹ Hence, it may be difficult to make a specific aetiological diagnosis by studying the paraspinal muscles alone.

Probable neuropathic contribution to the pathophysiology of idiopathic head drop and camptocormia

Pennison–Besnier et al⁴⁵ described a 72 year old woman with a 16 month history of camptocormia, whose lumbar paravertebral muscle showed fibrosis, fatty infiltration of interfascicular septa, groups of angular atrophic fibres, nuclear bags, fibre type grouping on ATPase stain, core, and target fibres. They think that denervation of the paraspinal muscles from impingement of the dorsal rami by osteoarthritic facet joints causes camptocormia. They asserted that the paraspinal muscle biopsies of other reports and two of their patients might not have shown typical neurogenic changes because they were performed late in the course of the illness. However, as already mentioned, neurogenic changes on muscle biopsy are common in elderly people and may not be clinically significant.^51,52 This is especially true in the cervical and lumbar paraspinal muscles, where there is a high incidence of degenerative vertebral disease in elderly people. Furthermore, to cause significant weakness of spinal extension large segments of the paraspinal muscles need to be denervated as sectioning of C1-C6 dorsal branches in patients with spasmodic torticollis⁵³ does not cause any functional impairment. In addition, although spondylosis could conceivably damage neural elements by vascular compromise, either from arterial ischaemia at the watershed region of the spinal arteries of Adamkiewicz or venous congestion, direct impingement of spinal roots have not been reported in patients with idiopathic head ptosis and camptocormia (tables 3 and 4). Therefore it is more likely that chronic denervation of the paraspinal muscles is a contributing factor rather than the basis for the development of idiopathic head ptosis and camptocormia.

The presence of pain, relatively acute onset, and recovery of head drop over a period of weeks in some patients is reminiscent of the clinical course of brachial neuritis (Parsonage-Turner syndrome). Indeed the clinical diversity of this condition has been well documented,^54,55 including involvement of structures as proximal as the roots. Kidron et al had reported C6 root involvement with paraspinal denervation.⁵⁶ Whether a similar process can selectively involve the cervical plexus and the dorsal spinal nerves can only be confirmed by studying the histology of paraspinal muscles and dorsal spinal nerves early in the course of the illness.

HEAD PTOSIS AND CAMPTOCORMIA: PARTS OF A SPECTRUM?

In most instances head drop and camptocormia are not related. It is rare to find a patient with both disorders except in extrapyramidal disorders such as MSA and postencephalitic parkinsonism.²³ However, the similarities between them (table 5) suggest that both head ptosis and camptocormia may occur as a result of similar pathophysiological processes affecting paraspinal muscles of different parts of the spine. In any individual patient local factors such as chronic denervation and loss of tissue elasticity may determine the spinal segment involved.

In summary, head ptosis and camptocormia include a diverse group of disorders that share in common involvement of different parts of the spine resulting in disabling anterior curvature of the spine. In addition to the known causes of flexion deformity of the spine, such as myasthenia gravis, amyotrophic lateral sclerosis, and Parkinson's disease, multiple cumulative age related factors such as loss of muscle tone, tissue elasticity, chronic stretch and denervation of the paraspinal muscles from degenerative spinal disease, may be involved in the pathogenesis. In practice, neuromuscular and extrapyramidal disorders, because of therapeutic and prognostic implications, should be ruled out in all patients. Measures to prevent fixed deformities—for example, passive mobilisation of the spine and the use of supports such as corsets and stiff collars—should be instituted early. At least some patients with idiopathic head drop recover partial function spontaneously. There is no clearly defined role for immunosuppressive or other pharmacotherapy. The case report of valproate induced reversible camptocormia introduces the intriguing possibility of using a GABA agonist in cases with an apparent extrapyramidal aetiology. Patients whose head ptosis does not improve should be considered for cervical fusion, which allows the patient to maintain a functionally useful head position.