No full-text available
To read the full-text of this research,
you can request a copy directly from the authors.
Severe Chin-on-Chest Cervical Spine Deformity in the Setting of Stiff-Person Syndrome: A Case Report
Abstract
Case:
Stiff-person syndrome (SPS) presents with progressive muscle rigidity, postural instability, and periodic debilitating spasms. Reports of axial hyperextension exist, but kyphotic deformities have not been described. We surgically treated a patient with debilitating SPS and severe cervicothoracic hyperkyphosis with posterior spinal fusion and instrumentation. At 1-year follow-up, the patient displayed better upright gait and forward gaze, 18° cervical lordosis, and improved patient-reported outcome scores.
Conclusion:
SPS can lead to extreme spinal deformity and disease, including hyperkyphosis of the cervicothoracic spine, and can successfully be managed with a multidisciplinary team and a posterior-only correction with spinal instrumentation and fusion.
ResearchGate has not been able to resolve any citations for this publication.
Stiff-person syndrome (SPS) is characterised by progressive rigidity and muscle spasms affecting the axial and limb muscles. Since its initial description in 1956, marked progress has been made in the clinical characterisation, understanding of pathogenesis and therapy of this disorder. SPS can be classified according to the clinical presentation into classic SPS and SPS variants: focal or segmental-SPS, jerking-SPS and progressive encephalomyelitis with rigidity and myoclonus. Most patients with SPS have antibodies directed against the glutamic acid decarboxylase, the rate-limiting enzyme for the production of the inhibitory neurotransmitter γ-aminobutyric acid (GABA). Antibodies directed against GABAA receptor-associated protein, and the glycine-α1 receptor can also be observed. Paraneoplastic SPS is commonly associated with antiamphiphysin antibodies and breast cancer. Treatment of SPS with drugs that increase the GABAergic tone combined with immunotherapy can improve the neurological manifestations of these patients. The prognosis, however, is unpredictable and spontaneous remissions are unlikely.
Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.
Background:
A 28-year-old woman presented to hospital after an episode of severe lower back spasms that occurred during a stressful family gathering. She had a history of progressive difficulty bending forward and increasing lumbar lordosis.
Investigations:
Physical examination, spine MRI scan, abdominal and pelvic ultrasound, electromyogram, nerve conduction studies, cerebrospinal fluid analysis, breast examination, Pap smear, transabdominal and endovaginal ultrasound.
Diagnosis:
Stiff-person syndrome with high titer of antibodies against glutamic acid decarboxylase.
Treatment:
Benzodiazepines and intravenous immunoglobulins.
Stiff person spectrum disorders (SPSD) are a broad group of immune-mediated disorders. Clinical presentations include classical stiff person syndrome (SPS), focal SPS, and progressive encephalomyelitis with rigidity and myoclonus (PERM). The most frequently associated antibodies are anti-GAD65, anti-GlyR, anti-amphiphysin, and anti-DPPX. Immunotherapy is the primary treatment modality. We present an illustrative case series of three patients: anti-GlyR antibody-mediated PERM presenting as rapidly progressive dementia; anti-amphiphysin antibody-mediated SPS; and SPS presentation with anti-Zic4 antibodies, spasmodic laryngeal stridor and fluctuating eyelid ptosis. Clinical characteristics, CSF findings, neurophysiological features, adequate immunological assays and a high suspicion index are essential for prompt diagnosis and management.
Introduction:
Stiff-person syndrome (SPS), first described in 1956 by Moersch and Woltman, is a progressive autoimmune disorder with core features of chronic fluctuating progressive truncal and limb rigidity and painful muscle spasms leading to gait difficulties, falls and an appearance that resembles tin soldiers. The syndrome is a rare, highly disabling disorder of the central nervous and frequently results in significant disability. Understanding of the etiology, clinical spectrum, diagnostic workup and therapeutic modalities for this painful and disabling disorder has vastly evolved over the past few years with more confidence in classifying and treating the patients. The purpose of this review is to increase the awareness, early detection, and treatment of this disabling disease.
Method:
PubMed was searched, all date inclusive, using the following phrases: stiff person syndrome,anti-Glutamic acid decarboxylase (Anti-GAD) antibody syndrome, Progressive encephalomyelitis with rigidity and myoclonus (PERM), and Paraneoplastic Stiff Person syndrome. No filters or restrictions were used. A total of 888 articles were identified.
Results:
The results were narrowed to 190 citations after excluding non-English and duplicate reports. Clinical presentation, laboratory testing, treatment, and prognosis were categorized and summarized.
Discussion:
In this article we will discuss the epidemiology, presentation and classification. Explain the pathophysiology of SPS and the autoimmune mechanisms involved. Discuss the diagnostic approach and treatments available, as well as, the prognosis and outcome.
Glutamic acid decarboxylase antibodies (GADAs) have been detected in patients with epilepsy, but the clinical determinants of epilepsy associated with GADA have not been defined.
We analyzed GADA with a radioimmunoassay in sera of 253 well-characterized patients with epilepsy and 200 control subjects. The positive samples were confirmed by immunohistochemistry and western blotting (WB). Sera were screened for other autoantibodies.
GADA were detected in 15 patients (5.9%) and in three control subjects (1.5%) (p = 0.026). Seven patients (2.8%) had high GADA titers [>or=1,000 relative units (RUs)/ml], six of whom had temporal lobe epilepsy (TLE). All three GADA-positive control subjects had low titers. Two of the five patients with high GADA titers and available cerebrospinal fluid (CSF) samples had intrathecal synthesis (IS) of GADA; one patient had CSF oligoclonal bands. The prevalence of increased levels of GADA tended to be higher in patients with TLE than in patients with extra-TLE [odds ratio (OR) 1.32, 95% confidence interval (CI) 0.39-4.42; p = 0.657]. The patients with high GADA titers had significantly higher number of other autoantibodies compared to the patients with low GADA titers (p = 0.001) and the patients with normal GADA (p < 0.001).
High GADA titers were present in a subgroup of patients; close to 90% had TLE. The immunologic profile of these patients suggests that the most probable origin of their epilepsy is autoimmune. A positive IS of GADA may be a marker of an ongoing immune response that could identify those patients in whom a trial with immunosuppressive therapy might be warranted.
Stiff person syndrome (SPS) varies from mild to severe, but if untreated it can be progressive and disabling. Although progress has been made in understanding and treating SPS, the disease remains underdiagnosed, delaying treatment. Antibodies against glutamic acid decarboxylase provide an excellent diagnostic marker, but their role in disease pathogenesis is uncertain. Research focused on identifying new autoantigens has provided evidence that gamma-aminobutyric acid (GABA)(A) receptor-associated protein (GABARAP), a 14-kD protein localized at the postsynaptic regions of GABAergic synapses, is an antigenic target. Circulating anti-GABARAP antibodies that inhibit GABA(A) receptor expression on GABAergic neurons have been found in up to 65% of SPS patients. The impairment of GABAergic pathways and reduction of brain GABA results in clinical manifestations of stiffness, spasms, and phobias. Increased awareness of SPS among practicing physicians is necessary to recognize the disease early and prevent permanent disability. Most patients with SPS respond to GABA-enhancing drugs, but the high doses required cause unacceptable adverse effects. The disease clearly responds to intravenous immunoglobulin, but repeated infusions are needed to maintain response. New immunomodulating agents are being explored to treat difficult cases and to induce long-lasting remissions.
Following several months of low back pain, a 36-year-old man developed progressive stiffness of the abdominal, low back, and thigh muscles. On examination, these muscles demonstrated marked hypertonia consistent with the clinical diagnosis of stiff-person syndrome. The patient demonstrated increased lumbar lordosis and had focal hyperhidrosis at different sites. Electromyography showed continuous activity of the paraspinal and thigh muscles, and serum and cerebrospinal fluid antibodies to glutamic acid decarboxylase (GAD) were markedly elevated. Diazepam and Lioresal offered partial pain relief. Paraspinal muscle administration of botulinum toxin A reduced the tone of paraspinal and thigh muscles significantly and resulted in marked improvement of ambulation and cessation of pain.
Stiff-person syndrome was diagnosed in a patient with chronic low back pain. The diagnosis of this rare neurological condition rests mainly on the clinical findings of axial and proximal limb rigidity, increased lumbar lordosis often accompanied with pain, and normal neurological findings apart from brisk deep tendon reflexes. Electromyography of the lumbar paraspinal muscles shows motor unit firing at rest with normal appearance of the motor unit potentials. Titers of antibody to glutamic acid decarboxylase are elevated. Diazepam is the treatment of reference. Physical therapy can substantially improve quality of life.