The dropped head syndrome with chronic inflammatory demyelinating polyneuropathy

The dropped head syndrome occurs in a variety of neuromuscular disorders. We present a woman with chronic inflammatory demyelinating polyneuropathy who developed this syndrome, likely reflecting severe demyelination of nerves to cervical paraspinal muscles. © 1994 John Wiley & Sons, Inc.     

Facioscapulohumeral muscular dystrophy presenting with isolated axial myopathy and bent spine syndrome

Several subtypes of facioscapulohumeral muscular dystrophy (FSHD) with atypical clinical presentation have been described. We report a new, distinct phenotype with progressive bent spine syndrome solely affecting the paraspinal muscles. Magnetic resonance imaging study of the lumbar spine revealed marked atrophy of the paraspinal muscles. The diagnosis was confirmed by DNA testing, which revealed shortened restriction fragments of the D4Z4 repeat on haplotype A in connection with a positive family history. Muscle Nerve 42:273–275, 2010     

The dropped head plus syndrome: quantitation of response to corticosteroids

Severe neck extensor weakness causes the dropped head syndrome and is a disabling symptom of many specific disorders. When a diagnosis cannot be established, it has been considered a manifestation of a restricted noninflammatory myopathy. A 44‐year‐old man presenting with dropped head and subsequent severe limb weakness did not respond to a first trial of corticosteroids but responded well to a subsequent prolonged trial of azathioprine followed by prednisone. The decision to persist with the second trial of treatment was prompted by documented sequential increases in lean body and muscle mass, and an improvement in the quantitative myometry score which preceded clinically obvious improvement. While mechanical damage to overstretched cervical paraspinal muscles is thought to preclude a response to treatment, cases of unexplained dropped head syndrome may merit consideration of prolonged immunosuppressant treatment. © 1999 John Wiley & Sons, Inc. Muscle Nerve 22: 115–118, 1999     

A new treatment regimen with high-dose and fractioned immunoglobulin in a special subgroup of severe and dependent CIDP patients

Background: Chronic inflammatory demyelinating polyneuropathy (CIDP) is treated with intravenous immunoglobulins (IVIg), corticosteroids or plasma exchange (PE). IVIg dosage is not universal and markers for treatment management are needed. Methods: We report the response to high-dose and fractioned IVIg in a subgroup of definite CIDP patients, resistant to corticosteroids and PE, responders to IVIg but with an efficacy window <15 d. Results: Four patients were included with similar predominantly clinical motor form and conduction abnormalities. Treatment management consisted of fractioning IVIg and increasing the monthly cumulated dose (mean: 3 g/kg/month). Serum IgG concentration was measured and correlated to the clinical state. Monitoring of serum IgG helped to guide IVIg administration dosage and frequency. A mean of 10 months was required to improve symptoms; therapy was then switched to subcutaneous (SC) route (maintenance dose: 3.5 g/kg/month). The mean Overall Neuropathy Limitations Scale was improved from 11 to 3.2 and the mean Medical Research Council scale from 26 to 90. Conclusion: It is important to distinguish patients with short IVIg efficacy window from those with classical resistance since the former may benefit from fractioning and increasing the IVIg dose. The monitoring of serum IgG level and its correlation to the clinical response could be of help in monitoring each individual's dosage.     

High-dose intravenous immunoglobulin for the treatment of MuSK antibody-positive seronegative myasthenia gravis

We treated two patients with anti-muscle specific tyrosine kinase (MuSK)-antibody positive seronegative myasthenia gravis (MG) with high-dose intravenous gammaglobulin (IVIg) and evaluated their clinical courses. Both patients were Japanese women, MuSK-positive seronegative MG, and were unresponsive to conventional treatments, including thymectomy, steroids, and tacrolimus. The patients required frequent hospitalization for plasmapheresis. In case 1, a 45-year-old woman, it was difficult to obtain blood access for plasmapheresis. High-dose IVIg, 400 mg/kg per day for 5 days, was administered in cases 1 and 2. In both cases, clinical improvement was observed 3 days after the start of IVIg therapy and lasted for 2 to 3 months. We propose that IVIg therapy is an effective treatment for MuSK-positive seronegative MG, when conventional treatments have failed.     

Resolution of chronic inflammatory demyelinating polyneuropathy-associated central nervous system lesions after treatment with intravenous immunoglobulin

Chronic inflammatory demyelinating polyneuropathy (CIDP) is a condition affecting the peripheral nervous system; however, it has been associated with central nervous system (CNS) involvement. The natural history and response to treatment of these CNS lesions are unknown. We report the case of a patient with CIDP which met research criteria for definite CIDP and associated symptomatic CNS lesions. She had resolution of her CNS-based clinical and radiographic findings with intravenous immunoglobulin (IVIG) therapy. IVIG is a reasonable treatment option when symptomatic, CIDP-associated CNS lesions are present.     

Long-term follow-up of Lambert-Eaton syndrome treated with intravenous immunoglobulin

Recent reports have shown that patients with Lambert-Eaton myasthenic syndrome (LEMS) improve transiently after high-dose intravenous immunoglobulin (IVIG) administration. Information about the usefulness of IVIG for long-term treatment is rather scanty. Our findings demonstrate the efficacy of monthly IVIG courses at a dose of 0.4 g/kg/day for 5 days, in a 41-year-old patient with LEMS without detectable malignancy. Improvement in limb strength, peak expiratory flow rate, and electrophysiological parameters, as well as clinical signs following IVIG, was evident as early as 7 days after the first course and is still maintained at 24-months follow-up. © 1997 John Wiley & Sons, Inc. Muscle Nerve, 20, 674–678, 1997.     

Two children with "dropped head" syndrome due to lamin A/C mutations

LMNA-related congenital muscular dystrophy (L-CMD) is a recently described disorder characterized by infantile-onset myopathy due to mutations in the lamin A/C (LMNA) gene. We report the genetic and clinical characteristics of two unrelated L-CMD patients. Patient 1 harbored a novel, L35P mutation and patient 2 a previously reported R249W mutation. The striking phenotype associated with L-CMD is important to recognize, as molecular diagnostic testing can spare patients unnecessary procedures and prompt the physician to monitor for associated cardiac arrhythmias.     

Restabilization treatment after intravenous immunoglobulin withdrawal in chronic inflammatory demyelinating polyneuropathy: Results from the pre‐randomization phase of the Polyneuropathy And Treatment with Hizentra study

In patients with chronic inflammatory demyelinating polyneuropathy (CIDP), intravenous immunoglobulin (IVIG) is recommended to be periodically reduced to assess the need for ongoing therapy. However, little is known about the effectiveness of restabilization with IVIG in patients who worsen after IVIG withdrawal. In the Polyneuropathy And Treatment with Hizentra (PATH) study, the pre‐randomization period included sudden stopping of IVIG followed by 12 weeks of observation. Those deteriorating were then restabilized with IVIG. Of 245 subjects who stopped IVIG, 28 did not show signs of clinical deterioration within 12 weeks. Two hundred and seven received IVIG restabilization with an induction dose of 2 g/kg bodyweight (bw) IgPro10 (Privigen, CSL Behring, King of Prussia, Pennsylvania) and maintenance doses of 1 g/kg bw every 3 weeks for up to 13 weeks. Signs of clinical improvement were seen in almost all (n = 188; 91%) subjects. During IVIG restabilization, 35 subjects either did not show CIDP stability (n = 21, analyzed as n = 22 as an additional subject was randomized in error) or withdrew for other reasons (n = 14). Of the 22 subjects who did not achieve clinical stability, follow‐up information in 16 subjects after an additional 4 weeks was obtained. Nine subjects were reported to have improved, leaving a maximum of 27 subjects (13%) who either showed no signs of clinical improvement during the restabilization phase and 4 weeks post‐study or withdrew for other reasons. In conclusion, sudden IVIG withdrawal was effective in detecting ongoing immunoglobulin G dependency with a small risk for subjects not returning to their baseline 17 weeks after withdrawal.     

Effect of the short and intensive rehabilitation (SHAiR) program on dynamic alignment in patients with dropped head syndrome during level walking

The purpose of this study was to assess the change of dynamic alignment after the short and intensive rehabilitation (SHAiR) program in patients with dropped head syndrome (DHS). Eighteen patients with DHS patients who complained of their inability to maintain horizontal gaze and underwent the SHAiR program. Patients performed level walking at a self-selected speed. Spatiotemporal, kinematic, and kinetic data were recorded using a three-dimensional motion analysis system. Statistical analysis was performed to compare these data before and after the SHAiR program. Those who underwent the SHAiR program showed a significant increase in the head angle and stride length compared to pre-treatment measurements (p < 0.05). The SHAiR program modifies the malalignment of the head and neck and spatiotemporal parameters in DHS patients during level walking.     

Histopathological analysis of skeletal muscle in patients with Parkinson's disease and ‘dropped head’/‘bent spine’ syndrome

Background‘Dropped head’ and ‘bent spine’ phenomena are recognized clinical presentations of neuromuscular disorders. Similar symptoms are known in patients with parkinsonian syndromes, but their pathophysiology remains unclear. One hypothesis is a relation between the movement disorder and the skeletal muscle pathology.MethodsWe describe detailed histopathological data from 19 consecutive skeletal muscle biopsies in patients with idiopathic Parkinson's disease (PD) and concomitant ‘dropped head’ or ‘bent spine’ syndrome. A biochemical analysis of the respiratory chain complexes was also performed, and clinical, electrophysiological, and imaging data were analyzed.ResultsThe subjects developed neuromuscular symptoms 2.7 ± 2.4 years after onset of PD. We found no correlation with the age at onset of the disease, disease duration, or severity. We found no evidence for dystonia nor did we find any relationship between their anti-parkinsonian medication, and possible drug side effects. Muscle biopsies were abnormal in all patients. Based on histopathological criteria we divided the muscle pathology into three different groups, i.e. necrotizing myopathy, inflammatory myopathy, and myopathy with mitochondrial abnormalities. Biochemical analysis of respiratory chain complexes revealed abnormalities in nine patients.Conclusions‘Dropped head’ and ‘bent spine’ symptoms in association with PD appear to be accompanied by a wide spectrum of histopathological abnormalities in skeletal muscle. A muscle biopsy should be performed to identify potentially treatable conditions (i.e. inflammatory myopathies).     

Thrombosis complicating high dose intravenous immunoglobulin: report of three cases and review of the literature

High dose intravenous immunoglobulin (IVG) is increasingly used in a broad range of immune mediated diseases. Thrombosis was exceptionally reported as a complication of this therapy. We describe three cases of thrombotic complications during or soon after IVIG treatment: myocardial infarction in a man and cerebral infarctions in an elderly man, associated with peripheral ischemia in a woman. In addition we review the published cases in the literature and discuss the possible etiologic factors.     

Efficacy and tolerability of different brands of intravenous immunoglobulin in the maintenance treatment of chronic immune‐mediated neuropathies

High‐dose intravenous immunoglobulin (IVIg) is effective in chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) and multifocal motor neuropathy (MMN). Not all brands of IVIg are however licensed for these neuropathies. We reviewed six patients with CIDP and seven with MMN treated with maintenance therapy with IVIg from 2009 to 2013. In all patients, we measured the Medical Research Council (MRC) and Overall Neuropathy Limitation Scale (ONLS) scores before each infusion, registered the monthly dose and brand of IVIg, and recorded adverse events. Patients were treated for 25–60 months (mean 49 months) alternating different brands of IVIg including IgVena, Gammagard, Kiovig, and Flebogamma. Minor and transient side effects were equally observed with each brand. No difference in the MRC or ONLS scores was observed in relation to the brand of IVIg used. Chronic maintenance treatment with IVIg in patients with MMN and CIDP was not associated with a different tolerability or efficacy despite the use of different brands of IVIg.     

A novel trial design to study the effect of intravenous immunoglobulin in chronic inflammatory demyelinating polyradiculoneuropathy

Using a novel trial design, we prospectively examined the effect of intravenous immunoglobulin in seven patients with chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) in a doubleblind, placebo-controlled cross-over study. We suggest that the commonly used manual muscle testing and Rankin scale are not sufficiently sensitive to measure changes in CIDP and should not be used as isolated outcome measures. We propose a timed 10-m walk, the Nine-Hole Peg Test, the Hammersmith Motor Ability Score, and myometry as alternative measures which are valid, reliable and sensitive. Our trial design permitted the measurement of a treatment response in three responders despite different patterns of disability typical of the broad clinical picture seen in CIDP.     

Establishment of a novel rehabilitation program for patients with dropped head syndrome: Short and intensive rehabilitation (SHAiR) program

The pathophysiology of dropped head syndrome (DHS) remains unknown, and its treatment algorithm and indication are not standardized. Here, we established a novel rehabilitation program, short and intensive rehabilitation program for DHS (SHAiR program), consisting of cervical paraspinal muscles exercise, range of motion exercise, cervical and thoracic mobilization, deep cervical flexor muscle exercise, hip lift exercise, anterior pelvic tilt exercise, and walking exercise. The aim of this study was to evaluate the clinical effectiveness of this program. We reviewed clinical outcomes for five consecutive patients with DHS who underwent the SHAiR program (SHAiR group). The outcomes were compared with those of other five patients with DHS who received exercise instruction (control group). Demographic data, the duration from onset of DHS, the apex of sagittal kyphosis on the lateral radiographs, and clinical outcomes including the ability to maintain normal horizontal gaze, chin brow vertical angle, and numerical rating scale (NRS) were evaluated at the initial visit and final follow-up at 7.5 months. There was no significant difference between the two groups in terms of demographic and radiographic data. The ability of horizontal gaze and NRS of cervical pain improved rapidly for all five patients in the SHAiR group as compared to no improvement for all patients in the control group. Rehabilitation for DHS was considered effective not only for localized rehabilitation such as exercise for training cervical extensor muscle function but also exercises for thoracolumbar posture improvement and the psoas muscle.     

Autopsy findings in the early stage of amyotrophic lateral sclerosis with “dropped head” syndrome

Dropped head syndrome (DHS) has been rarely observed in amyotrophic lateral sclerosis (ALS), and the neuropathological findings of this condition have almost never been described. The identification of transactivation response DNA‐binding protein 43 kDa (TDP‐43), which binds to RNA/DNA has provided a new method for studying ALS and frontotemporal lobar degeneration (FTLD). Post‐mortem examination of an adult sudden death case of a 71‐year‐old patient who complained of DHS exhibited severe loss of anterior motor neurons in the cervical cord (C4‐6). Loss of nerve fibers of the anterior roots was striking compared with posterior roots, together with marked neurogenic atrophy of posterior muscles semispinalis cervicis. Bunina bodies were found in large neurons of Betz giant cells, but not in the motor neurons of spinal cords, or neurons of bulbar regions. Phosphorylated TDP‐43 (p‐TDP‐43)‐positive structures were detected in the residual neurons of the cervical, thoracic and lumber cords, hypoglossal nucleus, cerebellar dentate nucleus and parahippocampal cortex, together with ubiquitin‐positive inclusions. Phosphorylated Tau positive structures in neuronal cytoplasm were found in the amygdala, entorhinal cortex and parahippocampal cortex, some of which co‐expressed p‐TDP‐43. The medial zone of cervical cords may be the first onset site, and that is the cause of head drop in the early stage of ALS. In spite of detailed examination, the direct cause of sudden death was not verified. This autopsy report revealed the relation of DHS which is a rare clinical manifestation of ALS, and neuropathological findings.