One in a Million: A Case Report of Stiff Person Syndrome

Stiff person syndrome (SPS) is a rare autoimmune disease caused by lack of inhibition to excitatory neurotransmitters in the central nervous system (CNS) leading to inappropriate motor unit firing. The pathophysiology is incompletely understood; however, high titers of antiglutamic acid decarboxylase antibody (anti-GAD Ab) are strongly associated with this disease. We present a 50-year-old woman with a history of ongoing gait and balance issues for 5 years with multiple negative workups. She recently had an acute exacerbation which left her bedbound, unable to move her legs or turn from side to side. After a negative workup at an outside hospital, the patient was discharged to a subacute rehabilitation facility. She then presented to our institution due to worsening of her condition and was ultimately diagnosed with SPS which was successfully treated. We review the case presentation and treatment options in the context of a severe disabling disease presentation.

Stiff Person Syndrome and Encephalitis with GAD Antibodies with Severe Anterograde Amnesia in an Adolescent: A Case Study and Literature Review

Antiglutamic acid decarboxylase (GAD65) encephalitis is rare and few pediatric cases have been reported, with variable clinical presentations. A 14-year-old female adolescent was managed in our department. She had been treated for several months for drug-resistant temporal lobe epilepsy and gradually presented major anterograde amnesia with confusion. Upon her arrival at the University Hospital Centre, she showed a classical form of stiff person syndrome. The brain magnetic resonance imaging showed bitemporal hyperintensities and hypertrophy of the amygdala. The blood and cerebrospinal fluid were positive for GAD65 antibodies. At 2 years of immunosuppressive treatment and rehabilitation, the course showed partial improvement of the memory and neuropsychiatric impairment, and epilepsy that continued to be active. GAD65 antibodies are associated with various neurological syndromes, and this presentation combining limbic encephalitis and stiff person syndrome is the first pediatric form published to date; there are also few cases described in adults.

Body Spasms in a Woman With Thyroid Disease

A 46-year-old woman with a history of autoimmune Hashimoto thyroiditis sought care for a 6-month history of spasms affecting her back and bilateral proximal lower extremities. On examination, the patient appeared anxious, and her whole body seemed to stiffen when the examiner entered the room. Her cognitive, cranial nerve, and upper extremity examinations were normal, except for brisk deep tendon reflexes. Examination of the patient’s spine indicated hyperlordosis of the lumbar region. There was visible hypertrophy of the lumbar paraspinal muscles. When asked to walk, the patient took short, tentative steps, despite having normal strength in her lower extremities. Her lower extremity tone demonstrated diffuse rigidity. Cerebrospinal fluid evaluation showed isolated increased protein concentration. Autoantibody testing of the serum and cerebrospinal fluid showed markedly increased levels of glutamic acid decarboxylase 65-kDa isoform–immunoglobulin G antibody in serum and in cerebrospinal fluid. Neurophysiologic studies in a movement disorders laboratory indicated a nonhabituating, exaggerated, acoustic startle response. Stiff-person syndrome was diagnosed. The patient received diazepam for symptomatic relief. At her follow-up visit, the patient reported reduction in frequency and severity of spasms but persistent stiffness throughout the lower back and lower extremities. Intravenous immunoglobulin was. After 3 months, the patient reported a 50% further improvement in stiffness and spasms but still required a walking aid. Physical therapy sessions focused on gait and safety, the patient was able to resume ambulation with a cane, without further falls. Stiff-person syndrome was described by Moersch and Woltman at Mayo Clinic in 1956. It most commonly arises in women of middle age but can affect men, women, and children. It is an autoimmune disorder of brainstem and spinal cord inhibitory interneuronal pathways, leading to what is termed central hyperexcitability.

Stiffness, Spasms, and Frequent Falls in a 41-Year-Old Man

A 41-year-old man sought care for 3 years of right-sided muscle stiffness. He also had 5- to 10-minute episodes of severe muscle spasms. He noted development of daily episodes of sudden, severe stiffness, often triggered by unexpected stimuli (eg, a touch or loud sound). He started using a walker and stopped driving. He stopped working because of increasing difficulty with mobility and cognition. On neurologic examination, he had a Kokmen Short Test of Mental Status score of 28/38, with points lost for orientation, attention, calculation, and recall. Cranial nerve examination showed bilateral ptosis and hypometric saccadic eye movements. He had normal strength but diffuse rigidity with increased tone, most severe in the right lower extremity. Magnetic resonance imaging of the brain indicated right parietal postoperative changes (post hematoma evacuation). Electroencephalography showed dysrhythmia grade 1 over the right frontotemporal region (above the prior hematoma). Cerebrospinal fluid was inflammatory, with mildly increased protein concentration and supernumerary oligoclonal bands. Movement laboratory evaluation demonstrated an exaggerated startle and abnormal exteroceptive response consistent with central nervous system hyperexcitability. Neural-specific autoantibody testing was positive for glycine receptor α‎1 subunit-immunoglobulin G in both serum and cerebrospinal fluid. He was diagnosed with progressive encephalomyelitis with rigidity and myoclonus with positive glycine receptor α‎1 subunit-immunoglobulin G. Given the immune-mediated cause of progressive encephalomyelitis with rigidity and myoclonus, he was started on intravenous methylprednisolone and concurrent rituximab. The patient markedly improved. His anxiety was still severe, however, and required increased escitalopram and cognitive behavioral therapy to control. He was tapered off intravenous methylprednisolone and maintained on rituximab. His symptoms eventually resolved. He remained stable at 2-year follow-up after initiating immunosuppression. Progressive encephalomyelitis with rigidity and myoclonus is considered a variant of stiff-person syndrome. There is clinical overlap between progressive encephalomyelitis with rigidity and myoclonus and classic stiff-person syndrome, which are both characterized by central nervous system hyperexcitability with exaggerated startle, muscle rigidity, and painful spasms.

Stiff-person syndrome with sensorimotor polyneuropathy – case report

Stiff-person syndrome (SPS) is a rare disorder with an estimated prevalence in the general population of 1–2 cases/1,000,000. It is 2–3 times more common in females, with symptom onset at the age of 20–50 years in most cases. Although stiff-person syndrome is associated with antibodies against glutamic acid decarboxylase and amphiphysin, their presence is not necessary for the diagnosis. The treatment should be multidirectional and include immunomodulation, symptomatic treatment as well as monitoring and treatment of overlapping autoimmune, and surgery. We present a case report of a patient diagnosed with stiff-person syndrome overlapping with axonal and demyelinating sensorimotor polyneuropathy. The diagnostic workup indicated diabetes-related polyneuropathy. About 30% of patients diagnosed with stiff-person syndrome also have diabetes. Polyneuropathy alone is rarely reported to overlap with the disorder. In our opinion, polyneuropathy may have a beneficial effect on the clinical presentation of stiff-person syndrome.

Brain and Muscle Metabolic Changes by FDG-PET in Stiff Person Syndrome Spectrum Disorders

Objective: To report clinical characteristics and fluorodeoxyglucose positron emission tomography (FDG-PET) findings in the brain and muscles of individuals with stiff person syndrome (SPS) spectrum disorders (SPSSDs).Methods: Retrospective cohort study from 1997 to 2018 at Johns Hopkins Hospital identified 170 individuals with SPS or cerebellar ataxia (CA) associated with anti-glutamic acid decarboxylase (anti-GAD)-65 antibodies. Fifty-one underwent FDG-PET, with 50 involving the body and 30 with dedicated brain acquisition. The clinical and immunological profiles were extracted via medical record review. The brain scans were analyzed quantitatively using the NeuroQ software, with comparison with an averaged normal database. The body scans were reviewed qualitatively by a blinded nuclear medicine radiologist.Results: Mean age of symptom onset was 41.5 years (range 12–75 years). Majority were female (68%) and White (64%). Of the patients, 82% had SPS (majority being classic phenotype), and 18% had CA. Three had a paraneoplastic process. Forty-seven had serum anti-GAD, two with anti-amphiphysin, and one with anti-glycine receptor antibodies. Brain metabolic abnormalities were seen in both SPS and CA, with significant differences between the groups noted in the right superior frontal cortex, right sensorimotor cortex, left inferior parietal cortex, bilateral thalami, vermis, and left cerebellum. Of the patients, 62% demonstrated muscle hypermetabolism, most commonly bilateral, involving the upper extremities or axial muscles. Neither brain nor muscle metabolism was correlated with functional outcomes nor treatments.Conclusions: Metabolic changes as seen by FDG-PET are present in the brain and muscle in many individuals with SPSSD. Future studies are needed to assess whether FDG-PET can help aid in the diagnosis and/or monitoring of individuals with SPSSD.