A Stiff Person Syndrome Misdiagnosed as a Psychiatric Illness: A Case Report.

BACKGROUND: Stiff Person Syndrome (SPS) is a rare autoimmune neurological disorder which is often misdiagnosed. We report here a case of SPS with a long diagnosis delay. CASE: A 36-year-old man presented with an 11-year history of progressive stiffness and painful spasms of his both legs, with recent worsening of his condition over the last year resulting in a considerable difficulty of standing up and walking. As the patient developed phobic symptoms, he was considered as having a psychiatric illness and treated with antianxiety and antidepressant drugs. As no real improvement was observed, the patient was referred to internal medicine. Neurological examination showed paraspinal, abdominal and lower limbs muscle contraction with lumbar rigidity. These symptoms were associated to adrenergic symptoms: profuse sweating, tachycardia and high bloodpressure. Initial routine investigations revealed high blood glucose level. Polygraphic electromyographic (EMG) evaluation from paraspinal and leg muscles showed continuous motor unit activity in agonist and antagonist muscle. Electroencephalography and brain magnetic resonance imaging were normal. Immunologic tests according to radio immune assay technique revealed high level of serum anti-glutamic acid decarboxylase (anti-GAD65) antibodies. Diagnosis of autoimmune SPS was retained based on clinical, electrophysiological, and immunological findings. Pregabalin at the dose of 150 mg, three times a day was prescribed with satisfying response. CONCLUSION: SPS is supported by an autoimmune pathogenesis and anti-GAD antibodies seems to be very helpful when SPS is clinically suspected. Treatment of SPS is a challenge, given the scarcity of the syndrome and the absence of established recommendations.

Anaesthetic management of a patient with a unique combination of anti-N-methyl-D-aspartate receptor encephalitis and stiff-person syndrome.

Stiff-person syndrome (SPS) and anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis are rare paraneoplastic syndromes caused by antibodies that target the central nervous system. Here, we describe a 26-year-old woman who presented with psychosis, amnesia, rigidity and fever. After extensive diagnostic and laboratory workup, she was diagnosed with an ovarian teratoma which was causing the symptoms of anti-NMDAR encephalitis and SPS. The patient was successfully treated with laparoscopic removal of the ovarian tumour under general anaesthesia. She was placed on immunosuppressant medications preoperatively and postoperatively, and her symptoms gradually resolved. Although there are case reports regarding the anaesthetic management of SPS and anti-NMDAR encephalitis, our study is the first report of a patient afflicted with both conditions.

Reducing excess stiffness in Stiff Person Syndrome using CBT: A case study.

BACKGROUND: Stiff Person Syndrome (SPS) is a rare neurological condition, characterised by rigidity in the trunk and limbs. Comorbid anxiety is common and known to exacerbate stiffness. OBJECTIVE: This case study examines the extent to which psychological treatment of comorbid anxiety alleviated stiffness in a patient whose condition was exacerbated by social anxiety. METHODS: A patient was treated using cognitive behavioural therapy, focussing on reducing anxiety and therefore stiffness by addressing rumination, self-focussed attention, and distressing cognitions relating to walking in public. The patient's walking, stiffness, and anxiety were assessed during and post-therapy using questionnaires. RESULTS: Walking, stiffness, and anxiety improved during treatment. At five months' follow up, while the improvement in anxiety was maintained, walking and stiffness had deteriorated. The patient and his Neurologist felt that this deterioration was biological, rather than psychological in nature. CONCLUSIONS: This is the first published case where SPS has been ameliorated (albeit temporarily) using psychological therapy, and has important implications for future research and treatment.

Human IgG directed against amphiphysin induces anxiety behavior in a rat model after intrathecal passive transfer.

Stiff person syndrome with auto-antibodies against amphiphysin is characterized by muscular stiffness, spasms, and anxiety which is a less appreciated core symptom. Here, we report that intrathecal application of purified immunoglobulin G-antibodies against amphiphysin from one patient induce anxiety behavior in rats. Immunostaining demonstrated binding of anti-amphiphysin antibodies to brain structures which are associated with anxiety disorders, such as the amygdala. We propose that antibody-mediated amphiphysin deficiency may account for anxiety behavior in stiff person syndrome via presynaptic dysregulation of GABAergic pathways.

Human stiff-person syndrome IgG induces anxious behavior in rats.

BACKGROUND: Anxiety is a heterogeneous behavioral domain playing a role in a variety of neuropsychiatric diseases. While anxiety is the cardinal symptom in disorders such as panic disorder, co-morbid anxious behavior can occur in a variety of diseases. Stiff person syndrome (SPS) is a CNS disorder characterized by increased muscle tone and prominent agoraphobia and anxiety. Most patients have high-titer antibodies against glutamate decarboxylase (GAD) 65. The pathogenic role of these autoantibodies is unclear. METHODOLOGY/PRINCIPAL FINDINGS: We re-investigated a 53 year old woman with SPS and profound anxiety for GABA-A receptor binding in the amygdala with (11)C-flumazenil PET scan and studied the potential pathogenic role of purified IgG from her plasma filtrates containing high-titer antibodies against GAD 65. We passively transferred the IgG fraction intrathecally into rats and analyzed the effects using behavioral and in vivo electrophysiological methods. In cell culture, we measured the effect of patient IgG on GABA release from hippocampal neurons. Repetitive intrathecal application of purified patient IgG in rats resulted in an anxious phenotype resembling the core symptoms of the patient. Patient IgG selectively bound to rat amygdala, hippocampus, and frontal cortical areas. In cultured rat hippocampal neurons, patient IgG inhibited GABA release. In line with these experimental results, the GABA-A receptor binding potential was reduced in the patient's amygdala/hippocampus complex. No motor abnormalities were found in recipient rats. CONCLUSION/SIGNIFICANCE: The observations in rats after passive transfer lead us to propose that anxiety-like behavior can be induced in rats by passive transfer of IgG from a SPS patient positive for anti-GAD 65 antibodies. Anxiety, in this case, thus may be an antibody-mediated phenomenon with consecutive disturbance of GABAergic signaling in the amygdala region.

Anxious depression and the stiff-person plus syndrome.

OBJECTIVE: To present the case of a patient with anxiety and depressive symptoms who developed the clinical picture of stiff-person plus syndrome (SPS-plus). BACKGROUND: Before the onset of typical SPS symptoms, psychiatric symptoms (like depression and anxiety) may be prominent and as such misleading, resulting in the diagnosis of a psychiatric condition. METHOD: We describe the case of a woman who initially presented with anxious depression and remained resistant to treatment with different classes of antidepressants and additional therapy with lithium and atypical antipsychotics. RESULTS: Evidence of neurologic dysfunction and significantly increased levels of serum autoantibodies for glutamic acid decarboxylase supported the diagnosis of SPS. The patient appeared to benefit from short-term immunosuppressive therapy with methylprednisolone. CONCLUSIONS: The authors believe that anxious depression and SPS-plus seen in this patient are the result of the same underlying autoimmune process, together forming a unique syndrome. Anxious and depressive symptoms in SPS can be explained by alterations in GABAergic neurotransmission.

A patient with post-traumatic stress disorder developing stiff person syndrome: is there a correlation?

Stiff person syndrome (SPS) is an uncommon disorder characterized by progressive muscle stiffness, rigidity, and axial muscle spasms. It is presumed to be an autoimmune process, with glutamic acid decarboxylase antibodies present in most cases. Here, we present a case report of a patient diagnosed with post-traumatic stress disorder (PTSD) acquired by sexual trauma and by exposure to the severely wounded soldiers she attended as a nurse. Subsequently, she developed SPS confirmed by serology. The possibility of an association between PTSD and SPS is theorized, given their relationship to the GABAergic system. Further studies examining the relation between PTSD and SPS should be initiated.

A neuropsychological assessment of phobias in patients with stiff person syndrome.

A neuropsychological assessment was performed in 10 patients with stiff person syndrome (SPS) to determine whether their anxiety and phobic symptoms precede stiffness and spasms or represent a reaction to disability. No neurocognitive dysfunction was noted. Patients perceived fears and anxiety as realistic and caused by SPS rather than due to an inherent phobic neurosis.

Specific phobia is a frequent non-motor feature in stiff man syndrome.

OBJECTIVE: To investigate systematically the rate and type of phobia in stiff man syndrome and its variants, and to compare patients with stiff man syndrome with and without phobia for sociodemographic and neurological characteristics. METHODS: 43 consecutive patients with stiff man syndrome referred to a university department of neurology were assessed using the anxiety disorders interview schedule, revised (ADIS-R), a structured diagnostic interview for anxiety disorders, in addition to a full clinical neurological and psychiatric assessment. RESULTS: 19 patients (44.2%) developed task specific phobia--that is, fear and avoidance of situations difficult to master owing to the motor symptoms of stiff man syndrome (such as crossing streets). Three further patients (7%) had subthreshold phobia--that is, phobic anxiety without avoidance. There were no significant differences between patients with and without phobia in terms of age, illness duration, type of stiff man syndrome, antibody status, or frequency of falls. Patients with phobia were more likely to present with exaggerated startle responses and to have an initial misdiagnosis of psychogenic movement disorder. CONCLUSIONS: Specific phobia is a frequent non-motor symptom of stiff man syndrome. Early recognition is an important aid to correct diagnosis. The aetiology of phobia in stiff man syndrome is unknown. There is no evidence of a direct pathogenic role of autoantibodies directed against glutamic acid decarboxylase in the development of phobia.

Quality of life in stiff-person syndrome.

Stiff person syndrome (SPS) is a rare, chronic disorder characterized by painful spasm and stiffness. We investigated the quality of life (QoL) in SPS patients, and identified factors associated with impairment in patients' QoL. Twenty-four SPS patients (10 men, 14 women; mean age +/- S.D., 52.6 +/- 9.5 years) completed the medical outcomes study Short Form health survey (SF-36), the Beck Depression Inventory (BDI), and a questionnaire asking for sociodemographic and clinical details. Extent of the disease was assessed using a distribution of stiffness score. SPS patients showed markedly reduced mean scores for all dimensions of the SF-36 when compared to norms from the general population of the United Kingdom. QoL scores showed a strong correlation with the extent of the disease. Depression was a common finding; 14 of 24 patients had depressive symptoms as evidenced by the BDI. There was a significant and strong correlation between the BDI score and several SF-36 subscores. This is the first study to address QoL in patients with SPS. We have shown that SPS has a significant impact on patients' reported QoL. The association between depression and QoL highlights the importance of recognizing and treating depression in SPS.

Effect of treatment with intravenous immunoglobulin on quality of life in patients with stiff-person syndrome.

The therapeutic effects of intravenous immunoglobulin (IVIG) on the stiff-person syndrome (SPS) have been described exclusively in case reports or open-label studies in terms of clinical outcomes. We investigate whether IVIG improves quality of life (QoL) in the SPS. Six patients with the classic form of SPS completed a generic QoL instrument, the SF-36, and a Visual Analogue Scale (VAS) before treatment as well as 2 weeks after completion of a course of IVIG. There was significant improvement in the SF-36 subscores for pain, social functioning, general mental health, and energy-vitality with treatment. The VAS also improved significantly. We conclude that treatment with IVIG improves QoL in the SPS.

Stiff-man syndrome. Results of interviews and psychologic testing.

Thirteen patients with stiff-man syndrome (SMS) were studied with the Minnesota Multiphasic Personality Inventory (MMPI), the Self-Administered Alcoholism Screening Test (SAAST), the State-Trait Anxiety Inventory (STAI) profiles, and by telephone interviews. The mean MMPI, SAAST, and STAI were within normal limits; however, several patients had abnormal profiles. The results of telephone interviews revealed that 8 patients (62%) had been given at least 1 psychiatric diagnosis and 4 (31%) abused alcohol or were dependent on it. Two patients had a psychiatric diagnosis that preceded the onset of symptoms of SMS. The authors hypothesize that SMS patients have a gamma-aminobutyric acid deficiency or GABAergic neuron dysfunction that leads to psychiatric symptoms, including depression and chemical abuse. Clinicians treating patients with SMS must be alert to the possible presence of comorbid psychiatric illnesses in this patient population.

[Agoraphobia and "psychogenic"-attributed gait disorder as symptoms of "stiff-man" syndrome]. / Agoraphobie und "psychogen" anmutende Gangstörung als Symptome eines "stiff-man"-Syndroms (SMS).

We report on two patients with truncal rigidity and agoraphobia. The fear of crossing open places had been judged as psychogenic in both cases. The detection of positive GAD-antibodies led to our final diagnosis. Treatment with liquorphoresis and clonazepam or diazepam alone resulted in a prompt amelioration of the rigidity and, to a lesser extent, of the agoraphobia as well. The stiff-man syndrome has neurological and psychological aspects and shows one more facet of the syndrome of agoraphobia first described by Westphal.

Psychiatric consultations in stiff-man syndrome.

BACKGROUND: Stiff-man syndrome is a rare central nervous system disease first described nearly 40 years ago. Its cause has been attributed to both neurologic and psychiatric processes. In recent years, it has been accepted as a neurologic condition in which the gamma-aminobutyric acid (GABA) system malfunctions, probably because of an autoimmune process. Published reports that have described psychiatric manifestations of the disease have relied on descriptions of one or two cases and literature reviews. METHOD: We reviewed the medical records of 24 patients with confirmed stiff-man syndrome, 12 of whom had received psychiatric consultation. This review was done to better determine the psychiatric manifestations of stiff-man syndrome. RESULTS: Retrospective analysis of these 12 cases showed that the most common psychiatric symptoms were anxiety, depression, and alcohol abuse. CONCLUSION: We speculate that the GABA system is involved in both the neurologic and psychiatric symptoms of these patients. Psychiatrists have a significant role in the management of patients with stiff-man syndrome and may be expected to manage anxiety, depression, and substance misuse.

Psychological factors in the diagnosis and pathogenesis of stiff-man syndrome.

Retrospective psychological evaluation of nine patients with stiff-man syndrome (SMS), seven of whom evidenced autoimmune disease, revealed a characteristic set of psychological symptoms or features: Major stressful life events preceded the development of permanent symptoms by 6 months or less (seven patients); transient motor symptoms occurred in emotionally distressing situations months or even years before the onset of a permanent motor deficit (five patients); after onset, similar situations specifically precipitated or augmented stiffness and spasms (five patients). We also found task-specific fear resembling agoraphobia (six patients) and loss or invalidation of one or both parents, or loss of home, in childhood (seven patients). Eight patients were initially misdiagnosed as having psychogenic movement disorder. We conclude that the common misdiagnosis of SMS as a psychogenic movement disorder is due to the compelling association of a set of salient psychological features, bizarre and fluctuating motor symptoms, and lack of approved neurologic signs.