Stiff person syndrome (SPS) is a rare autoimmune neurological disorder that an orthopedic surgeon will encounter infrequently in their clinical practice. It presents with a diffuse increase in tone, rigidity, and stiffness of all muscles including the trunk due to contraction of the lumbar and abdominal muscles, which can be asymptomatic initially followed by a fixed posture (hyperlordosis). Painful muscle spasms are precipitated by auditory and tactile stimulation1. Falls are common due to severe spasms, resulting in fractures and dislocation2. Psychiatric issues such as fear, depression, and anxiety are very common in SPS, which severely affect the quality of life. These clinical features along with confirmation of continuous motor unit activity (CMUA) in agonist and antagonist muscles on electromyography (EMG), positive serology for glutamic acid decarboxylase 65 (GAD65) (-or amphiphysin-) autoantibodies, absence of other neurological disorders or cognitive impairment that could explain the stiffness, and response to benzodiazepines are needed to diagnose SPS3.
The patient was informed that data concerning the case would be submitted for publication, and he provided consent.
A 57-year-old man diagnosed with SPS 2 years ago presented to the orthopedics clinic with complaints of right groin pain, inability to bear weight, and gradual shortening of the right lower extremity over 3 months. He had no history of trauma or falls. Over the previous year, the patient had been hospitalized multiple times for spasm exacerbation. He was bed bound and unable to work because of severe whole body rigidity and elicitation of painful spasms with tactile stimulation. On initial neurological examination, he had diffuse increase in tone, with generalized hyperreflexia. Assessment of motor power was limited because of severe muscle spasms on touch. Magnetic resonance imaging (MRI) of brain and spinal cord was unremarkable. Cerebrospinal fluid analysis and blood workup were all normal and failed to reveal an infectious, metabolic, or paraneoplastic cause of his symptoms. Final diagnosis of SPS was made on the basis of a high serum titer of anti-GAD 65 antibodies and CMUA on EMG.
The patient was treated with a 5-day course intravenous immunoglobulin (IVIG). In the following weeks, he had significant improvement in rigidity and was able to mobilize with the help of stick. Muscle spasms were controlled with baclofen, clonazepam, and methadone.
Five months after the treatment with IVIG, he had another hospitalization for exacerbation and recurrent muscle spasms, and he developed severe right groin pain. This was treated symptomatically with increasing doses of benzodiazepines, baclofen, and tizanidine. The groin pain was attributed to severe muscle spasms at the time. Patient persisted to have right groin tenderness and gradual shortening of right lower limb with restricted hip joint motion. On examination in the orthopedics clinic, both lower extremities (right much more than left) were rigid with induction of muscle spasms on tactile stimulus. Pulses were palpable. Radiograph of the pelvis and right hip lateral view showed a displaced right neck of femur fracture (Figs. 1-A and 1-B). Pelvic MRI revealed right femoral neck fracture with adjacent reactive changes. There was no evidence of infection or underlying bony lesion to suggest a pathologic fracture (Figs. 2-A and 2-B). Inflammatory markers were unremarkable and serological testing was positive for GAD65 autoantibodies.
Primary total hip replacement was performed under regional anesthesia with sedation, through posterior approach. A 15-cm curved incision across the buttock was made, for a conventional posterior approach to the hip joint. Thickening and contractures of the articular capsule, fibrosis, and osteophytes were removed. Femur was broached with some difficulty and a cerclage wire was used prophylactically to prevent bony injury. The reduction of hip was extremely difficult despite a low neck cut. We therefore had to perform unusual soft tissue releases during the procedure. Tensor fascia lata was released followed by partial release of iliopsoas, adductor tendon, and extensive periacetabular capsulectomy. The joint was reduced with an implant with a shortest possible neck length successfully.
Postoperatively, patient was ambulated full weight-bearing and showed significant improvement in postoperative Harris Hip Score (HHS). Preoperative HHS was 34; at 1-month follow-up, the HHS was 84; at 15-month follow-up, HHS was 86; and at 24-month follow-up, HHS was 87.
In the postoperative period, the patient maintained regular neurological follow-up for complete optimization of medications to avoid dislocation of the repaired hip by recurrent spasms and rigidity. The latter symptoms were well controlled on high doses of baclofen, tizanidine, and clonazepam.
SPS is a rare autoimmune and at times paraneoplastic disorder4-6. Symptoms can present slowly with a mean age of onset at 42.2 (29 to 59) years and is more common in women than men. It is thought to be secondary to hyperexcitability at the brainstem and spinal cord levels mainly due to dysfunction of inhibitory pathways. Its pathogenesis was further explained after the discovery of anti-GAD antibodies. GAD is the enzyme involved in the rate limiting step for decarboxylation and formation of GABA, the main inhibitory enzyme of the central nervous system (CNS)7.
Antibodies directed against GAD result in inhibition of Gamma aminobutyric acid (GABA) synthesis and ultimately overall increase in the excitatory output in the CNS pathways7. The latter results in generalized hypotonia, simultaneous activation of agonist and antagonist muscles, severe muscles spasms, and abnormal postures8. Patients with SPS may also exhibit type 1 diabetes mellitus, oculomotor abnormalities, dysautonomia, and psychiatric symptoms8. Less than 10% patients can have paraneoplastic SPS secondary to antiamphiphysin antibodies. These are mostly observed in women with breast cancer8. Along with the presence of antibodies, EMG is a supportive test, which demonstrates CMUA in otherwise relaxed muscles and simultaneous activity in agonist and antagonists muscles.
Our patient had an insidious onset of SPS with classical findings of episodic aching and stiffness of axial muscles slowly progressing to proximal limb muscles. As the disease advanced, he experienced severe painful muscles spasms, limb rigidity, and abnormal posturing, resulting in severe gait disturbances and difficulty in walking. Progression to the thoracic muscles caused breathing difficulties with an emotionless, mask-like appearance due to facial muscle involvement. Characteristic EMG finding of CMUA and the detection of high titers of serum GAD65 antibodies confirmed the diagnosis of SPS. Recurrent, severe bouts of muscle spasms led to an atraumatic and nonpathological neck of femur fracture, unexpected and therefore overlooked. Despite the fact that the patient had multiple hospital admissions to control generalized body pains and severe muscles spasms, the etiology of severe lower extremity pain was overlooked and attributed in general to his disease. Stiffness combined with a painful hip resulted in severe disability and limitation of function including postural changes and routine activities of daily living.
The mainstay of treatment for SPS remains symptomatic, with the use of GABA agonists.
Despite being an autoimmune disorder, the response to traditional immunosuppressive agent is controversial. IVIG has shown to decrease spasms and rigidity, and improve mobility and quality of life in these patients and should be offered along with symptomatic control. IVIG, in theory, acts by clearing the circulating autoantibodies and also has an effect on immunomodulation9. The benefit can last from 6 weeks to 1 year. However, recurrent use of IVIG is often limited due to cost.
After initial diagnosis, our patient was treated with a course of IVIG with significant improvement of his symptoms. Following this, he underwent primary cementless total hip replacement performed by posterior approach under regional anesthesia. Surgery was uneventful with gradual but significant improvement recorded in the postoperative function (HHS). The foremost concern in the postoperative period was prevention of severe muscle spasms and rigidity. This was achieved with high doses of baclofen, clonazepam, and tizanidine. We also considered the use of Botox injections for local control of spasms; however, we were able to control symptoms with oral medications.
At 15-month follow-up, radiographs of the pelvis (anterior-posterior and lateral views) demonstrated right total hip prosthesis with no interval radiolucency around the femoral stem and acetabular cup or interval change in implant orientation (Figs. 3-A and 3-B and Figs. 4-A and 4-B, respectively).
At 20-month follow-up, the patient suffered from a relapse of symptoms of SPS, with severe generalized rigidity despite adequate medical management.
This was treated again with a second course of IVIG with a good response and restoration of mobility.
Femur neck fracture is a well-recognized surgical emergency. This was an unusual and overlooked presentation of an atraumatic, nonpathological femur neck fracture in a patient with a neurological disorder and stiffness. Even with widely accepted therapy with benzodiazepines and baclofen in SPS, refractory spasms contributed to significant forces on bony elements leading to a fracture. Primary total hip replacement for the neck of femur fracture is potentially difficult but reasonable operative procedure for SPS with neck of femur fracture.
1. Jachiet V, Laine L, Gendre T, Henry C, Da Silva D, de Montmollin E. Acute respiratory failure in a patient with stiff-person syndrome. Neurocrit Care. 2016;25(3):455-7.
2. T Chang, B Lang, A Vincent. Stiff person syndrome in South Asia. BMC Res Notes. 2016 9:468.
3. Levy LM, Dalaks MC, Floeter MK. The stiff-person syndrome: an autoimmune disorder affecting neurotransmission of gamma-aminobutyric acid. Ann Intern Med. 1999;131(7):522-30.
4. Bhatti A, Gazali Z. Recent advances and review on treatment of stiff person syndrome in adults and pediatric patients. Cureus. 2015;7(12):e427.
5. Pretorius E, Struwig W. Stiff person syndrome (SPS): literature review and case report. S Afr J Psych. 2013;19(4):228-31.
6. Henningsen P, Meinck HM. Specific phobia is a frequent non-motor feature in stiff man syndrome. J Neurol Neurosurg Psychiatry. 2003;74:462-5.
7. Dinkel K, Meinck HM, Jury KM, Karges W, Richter W. Inhibition of gamma-aminobutyric acid synthesis by glutamic acid decarboxylase autoantibodies in stiff-man syndrome. Ann Neurol. 1998;44(2):194-201.
8. Baizabal-Carvallo JF, Jankovic J. Stiff-person syndrome: insights into a complex autoimmune disorder. J Neurol Neurosurg Psychiatry. 2015;86(8):840-8.
9. Harding AE, Thompson PD, Kocen RS, Batchelor JR, Davey N, Marsden CD. Plasma exchange and immunosuppression in the stiff man syndrome. Lancet. 1989;2(8668):915.