Síndrome de persona rígida confundido por trastorno conversivo: un error común. caso clínico / Stiff-person syndrome mistaken for conversive disorder: a common error

Stiff-person syndrome is characterized by persistent muscle spasms, involving agonist and antagonist muscles simultaneously, starting in the lower limbs and trunk. It tends to occur in the fourth to sixth decade of life, presenting with intermittent spasms that later become continuous and usually painful. Minor sensory stimuli, such as noise or light touch, precipitate severe spasms. Spasms do not occur during sleep and only rarely involve cranial muscles. We present a case that for two years was diagnosed and treated as a conversion disorder associated with depression. After two years she was admitted to another hospital with an unmistakable picture of stiff-person syndrome with hypertrophy and rigidity of lower limb muscles, compatible electrophysiology and positive anti-GAD antibodies. She had autoimmune hypothyroidism, that should have raised the suspicion of stiff-person syndrome earlier. She responded to intravenous immunoglobulin and mycophenolate mofetil and and to tranquilizers that have muscle relaxant properties.

[THE ROLE OF AUTOANTIBODIES TO THE EXTRACELLULAR REGIONS OF IONOTROPIC RECEPTORS IN ETIOLOGY AND PATHOGENESIS OF AUTOIMMUNE DISEASES].

In the last years it was shown that autoantibodies to the extracellular regions of the ionotropic receptors, such as glutamate AMPA- and NMDA-receptors, GABAA-receptors, glycine and nicotinic acetylcholine receptors, induce a wide spectrum of autoimmune diseases, including limbic encephalitis, Rasmussen's encephalitis, systemic lupus erythematosus, myasthenia gravis, encephalomyelitis, and stiff-man syndrome. In the review the literature data concerning the autoimmune processes provoking autoantibodies formation to the ionotropic receptors, the epitopes participating in the induction of pathogenic autoantibodies, and the effects of these antibodies on the functions of nervous cells and their role in the development of autoimmune diseases were analyzed and systematized. The possible role of oncology diseases in the generation of autoantibodies to the ionotropic receptors was discussed. Approaches that are currently being developed to inhibit the synthesis of pathogenic autoantibodies and to their neutralization were considered. These approaches may be subsequently used to treat the autoimmune diseases caused by the antibodies to ionotropic receptors.

A Rare Case of Childhood Stiff Person Syndrome Associated With Pleuropulmonary Blastoma.

INTRODUCTION: Stiff person syndrome is a rare autoimmune, neurological disorder characterized by progressive rigidity and episodic painful spasms, predominantly affecting the proximal limbs and axial muscles, and leading to progressive disability. We report the case of a child who developed symptoms compatible with stiff person syndrome during treatment for pleuropulmonary blastoma. PATIENT DESCRIPTION: A 3-year, 5-month-old girl was admitted for gradually worsening postural tremor, painful spasms, and generalized stiffness. Since the age of 3 years, she had been on adjuvant chemotherapy for pleuropulmonary blastoma before surgical resection. Brain magnetic resonance imaging and electroencephalographic findings were normal. Although serologic tests for autoimmune disease, including paraneoplastic antibodies and antiglutamic acid decarboxylase antibodies, were unremarkable, her findings were attributed to a paraneoplastic syndrome based on her clinical features and medical history. However, following the planned pulmonary lobectomy, her symptoms were paradoxically aggravated, with continuous motor unit potential at rest on electromyography, which occurs in stiff person syndrome. She gradually improved during postadjuvant chemotherapy with simultaneous immunotherapy including intravenous immunoglobulins and methylprednisolone, and she had recovered completely when evaluated at the 22-month follow-up visit after completion of her treatment for pleuropulmonary blastoma. CONCLUSION: We present the first documented child with stiff person syndrome associated with pleuropulmonary blastoma. The marked clinical improvement following chemotherapy for pleuropulmonary blastoma was yet more proof of the pleuropulmonary blastoma-related stiff person syndrome. In children with a malignancy and stiff person syndrome, a paraneoplastic syndrome should be considered and the treatment for the malignancy must be undertaken.

Evidence of T-cell mediated neuronal injury in stiff-person syndrome with anti-amphiphysin antibodies.

Paraneoplastic stiff-person syndrome (SPS) has been associated with antibodies against amphiphysin. Current evidence supports a pathogenic role for anti-amphiphysin antibodies. A 74-year-old female was diagnosed with amphiphysin-associated paraneoplastic stiff-person syndrome and associated encephalomyelitis. She had initial response to IVIG, however her symptoms worsened after two months and were resistant to further treatment. Subsequently the patient died and a post-mortem was performed. Neuropathology revealed perivascular and parenchymal lymphocytic infiltrates, with neuronophagia mediated by CD8+ T cells and microglia in brainstem, spinal cord, and mesial temporal lobe structures. These findings suggest a pathogenic role of cytotoxic CD8+ T-cells, with potential implication for therapy of future patients.

Lower extremity predominant stiff-person syndrome and limbic encephalitis with amphiphysin antibodies in breast cancer.

A 54-year-old woman presented with several weeks of psychiatric symptoms, partial-onset seizures, and painful spasms of the lower extremities. On examination, she exhibited severe stiffness and intermittent extensor spasms of the lower extremities. Magnetic resonance imaging of the brain showed T2 hyperintensity in the left temporal lobe with enhancement after gadolinium administration on T1-weighted images. Amphiphysin antibodies were present in the serum. Radiographic screening for malignancy disclosed a metastatic breast cancer. The case is a unique example of amphiphysin autoimmunity, illustrating the possibility of paraneoplastic stiff-person syndrome and limbic encephalitis coexisting in a patient with a "classical" presentation of stiff-person syndrome confined to the lower extremities.

Stiff person syndrome-associated autoantibodies to amphiphysin mediate reduced GABAergic inhibition.

Synaptic inhibition is a central factor in the fine tuning of neuronal activity in the central nervous system. Symptoms consistent with reduced inhibition such as stiffness, spasms and anxiety occur in paraneoplastic stiff person syndrome with autoantibodies against the intracellular synaptic protein amphiphysin. Here we show that intrathecal application of purified anti-amphiphysin immunoglobulin G antibodies induces stiff person syndrome-like symptoms in rats, including stiffness and muscle spasms. Using in vivo recordings of Hoffmann reflexes and dorsal root potentials, we identified reduced presynaptic GABAergic inhibition as an underlying mechanism. Anti-amphiphysin immunoglobulin G was internalized into neurons by an epitope-specific mechanism and colocalized in vivo with presynaptic vesicular proteins, as shown by stimulation emission depletion microscopy. Neurons from amphiphysin deficient mice that did not internalize the immunoglobulin provided additional evidence of the specificity in antibody uptake. GABAergic synapses appeared more vulnerable than glutamatergic synapses to defective endocytosis induced by anti-amphiphysin immunoglobulin G, as shown by increased clustering of the endocytic protein AP180 and by defective loading of FM 1-43, a styryl dye used to label cell membranes. Incubation of cultured neurons with anti-amphiphysin immunoglobulin G reduced basal and stimulated release of γ-aminobutyric acid substantially more than that of glutamate. By whole-cell patch-clamp analysis of GABAergic inhibitory transmission in hippocampus granule cells we showed a faster, activity-dependent decrease of the amplitude of evoked inhibitory postsynaptic currents in brain slices treated with antibodies against amphiphysin. We suggest that these findings may explain the pathophysiology of the core signs of stiff person syndrome at the molecular level and show that autoantibodies can alter the function of inhibitory synapses in vivo upon binding to an intraneuronal key protein by disturbing vesicular endocytosis.

Neuropathology and binding studies in anti-amphiphysin-associated stiff-person syndrome.

The authors report a 71-year-old woman with amphiphysin-associated paraneoplastic stiff-person syndrome, opsoclonus, and encephalopathy. The patient's symptoms temporarily responded to plasmapheresis in parallel with a decline of serum anti-amphiphysin antibody titers. Later, the encephalopathy progressed rapidly and the patient died. Binding studies and the detection of autoantibodies in the patient's CNS as well as the treatment response suggest a pathogenic role of the anti-amphiphysin antibodies.

[Buschke adult scleroderma as a rare differential stiff-man syndrome diagnosis]. / Scleroedema adultorum Buschke als seltene Differentialdiagnose des Stiff-man-Syndroms.

Stiff-man syndrome is a rare disorder of the central nervous system characterized by muscular rigidity and superimposed spasms. The etiology is still unknown and an autoimmune cause is discussed. Many differential diagnoses of muscular rigidity and of induration of the skin have to be considered. A 22 year old patient was admitted under suspicion of a stiff-man syndrome. He has had developed a painful rigidity of the trunk, starting in the neck. Massive stiffness of the trunk with pale appearance of the skin and a beginning disorder of swallowing and respiration were observed. Clinical investigation, EMG, cerebrospinal fluid and laboratory findings were all normal, thus excluding a stiff-man syndrome and other neuromuscular diseases. Skin biopsy showed typical changes of Buschke's scleredema adultorum, a rare connective tissue disorder of unknown etiology. Therapy with corticosteroide and ciclosporin led to a mild improvement of symptoms. Although rare, Buschke's scleredema adultorum should be regarded as a differential diagnosis of the stiff man syndrome.

[Possible diagnostic error of "Bechterew disease"]. / Mögliche Fehldiagnose "Morbus Bechterew".

A 41-year old caucasian male presented with limited range of motion of the entire spine and myogenous intermittent claudication. He was referred with the diagnosis "ankylosing spondylitis". The clinical picture mimicked ankylosing spondylitis, but there were no corresponding radiological abnormalities despite a 13-year history of his disease. Laboratory values showed markedly elevated levels of muscle enzymes. The diagnosis of rigid spine syndrome, a subtype of muscular dystrophy, was made from the clinical picture a normal EMG and degenerative changes on a biopsy from the muscle trapezius. We would like to draw attention to this rare cause of back pain.