HSCT for stiff person syndrome and myasthenia gravis.

Recent advances in neuroimmunology have shed light on the pathogenic mechanisms underlying rare neuroimmunologic conditions such as myasthenia gravis (MG) and stiff person syndrome (SPS). Despite the rarity of these conditions, their complex manifestations and potential for irreversible disability necessitate effective therapeutic strategies. This chapter reviews the current understanding of the safety and efficacy of hematopoietic stem cell transplantation (HSCT) in MG and SPS. Several case reports and retrospective studies have demonstrated promising outcomes following HSCT in refractory MG and SPS, with significant clinical improvement and even discontinuation of chronic immunomodulatory therapy in some cases. Furthermore, HSCT may offer insights into the underlying pathophysiologic mechanisms of these conditions, particularly the role of cellular immunity. Although more research is needed to fully understand the impact of HSCT on disease pathology and outcomes, current evidence suggests that HSCT could be a valuable therapeutic option for patients with refractory MG and SPS.

[Stiff-Person Syndrome: Results of the First Nationwide Survey in Japan].

Stiff-person syndrome (SPS) is a rare autoimmune neurological disorder characterized by progressive axial muscle stiffness, central nervous system hyperexcitability, and painful stimulus-sensitive muscle spasms. A nationwide survey performed in 2018 showed the estimated prevalence of SPS was 0.2 per 100,000 population. Most patients with SPS had antibodies against glutamic acid decarboxylase 65, followed by antibodies to the glycine receptor α-subunit. Usually, patients with SPS showed favorable outcomes; however, some studies have reported intractable SPS. Early diagnosis and aggressive immunotherapy are necessary for management of patients with SPS.

Clinical features in antiglycine receptor antibody-related disease: a case report and update literature review.

Background and objectives: Antiglycine receptor (anti-GlyR) antibody mediates multiple immune-related diseases. This study aimed to summarize the clinical features to enhance our understanding of anti-GlyR antibody-related disease. Methods: By collecting clinical information from admitted patients positive for glycine receptor (GlyR) antibody, the clinical characteristics of a new patient positive for GlyR antibody were reported in this study. To obtain additional information regarding anti-GlyR antibody-linked illness, clinical data and findings on both newly reported instances in this study and previously published cases were merged and analyzed. Results: A new case of anti-GlyR antibody-related progressive encephalomyelitis with rigidity and myoclonus (PERM) was identified in this study. A 20-year-old man with only positive cerebrospinal fluid anti-GlyR antibody had a good prognosis with first-line immunotherapy. The literature review indicated that the common clinical manifestations of anti-GlyR antibody-related disease included PERM or stiff-person syndrome (SPS) (n = 179, 50.1%), epileptic seizure (n = 94, 26.3%), and other neurological disorders (n = 84, 24.5%). Other neurological issues included demyelination, inflammation, cerebellar ataxia and movement disorders, encephalitis, acute psychosis, cognitive impairment or dementia, celiac disease, Parkinson's disease, neuropathic pain and allodynia, steroid-responsive deafness, hemiballism/tics, laryngeal dystonia, and generalized weakness included respiratory muscles. The group of PERM/SPS exhibited a better response to immunotherapy than others. Conclusions: The findings suggest the presence of multiple clinical phenotypes in anti-GlyR antibody-related disease. Common clinical phenotypes include PERM, SPS, epileptic seizure, and paraneoplastic disease. Patients with RERM/SPS respond well to immunotherapy.

Successful use of anti-CD19 CAR T cells in severe treatment-refractory stiff-person syndrome.

Treatment with autologous chimeric antigen receptor (CAR) T cells has emerged as a highly effective approach in neuroimmunological disorders such as myasthenia gravis. We report a case of successful anti-CD19 CAR T cell use in treatment-refractory stiff-person syndrome (SPS). To investigate clinical and immunological effects of anti-CD19 CAR T cell use in treatment-refractory SPS, a 69-y-old female with a 9-y history of treatment-refractory SPS with deteriorating episodes of stiffness received an infusion of autologous anti-CD19 CAR T cells (KYV-101) and was monitored clinically and immunologically for more than 6 mo. CAR T cell infusion resulted in reduced leg stiffness, drastic improvement in gait, walking speed increase over 100%, and daily walking distance improvement from less than 50 m to over 6 km within 3 mo. GABAergic medication (benzodiazepines) was reduced by 40%. KYV-101 CAR T cells were well tolerated with only low-grade cytokine release syndrome. This report of successful use of anti-CD19 CAR T cells in treatment-refractory SPS supports continued exploration of this approach in SPS and other B cell-related autoimmune disorders.

Spinal cord stimulation for the symptomatic treatment of rigidity and painful spasm in a case of stiff person syndrome.

BACKGROUND: Stiff person syndrome (SPS) is a rare neuroimmunological disorder characterized by rigidity and painful spasm primarily affecting the truncal and paraspinal musculature due to autoimmune-mediated neuronal hyperexcitability. Spinal cord stimulation (SCS) is an approved therapy for managing painful neuropathic conditions, including diabetic peripheral neuropathy and refractory angina pectoris. We describe the novel use of SCS for the treatment of spasm and rigidity in a 49-year-old man with seropositive stiff person syndrome (SPS). The patient was treated with intravenous immunoglobulin (IVIG) and oral medications over a 13-month period with minimal improvement, prompting consideration of SCS. To our knowledge, this is the first report of the successful use of SCS in SPS with the demonstration of multifaceted clinical improvement. METHODS: Following a successful temporary SCS trial, permanent implantation was performed. Spasm/stiffness (Distribution of Stiffness Index; Heightened Sensitivity Scale; Penn Spasm Frequency Scale, PSFS), disability (Oswestry Disability Index, ODI; Pain Disability Index, PDI), depression (Patient Health Questionnaire-9, PHQ-9), sleep (Pittsburgh Sleep Quality Index, PSQI), fatigue (Fatigue Severity Scale, FSS), pain (Numerical Pain Rating Scale, NPRS), quality of life (EuroQoL 5 Dimension 5 Level, EQ-5D-5L), and medication usage were assessed at baseline, 6-month, and 10-month postimplantation. RESULTS: ODI, PHQ-9, FSS, NPRS, PSQI, and EQ-5D-5L scores showed a notable change from baseline and surpassed the defined minimal clinically important difference (MCID) at 6-month and 10-month follow-up. Oral medication dosages were reduced. CONCLUSIONS: The novel use of SCS therapy in seropositive SPS resulted in functional improvement and attenuation of symptoms. We present possible mechanisms by which SCS may produce clinical response in patients with SPS and aim to demonstrate proof-of-concept for a future comprehensive pilot study evaluating SCS-mediated response in SPS.

Successful Autologous Hematopoietic Stem Cell Transplant in Glycine Receptor Antibody-Positive Stiff Person Syndrome: A Case Report

BACKGROUND AND OBJECTIVES: To describe a case of glycine receptor (GlyR) antibody-positive stiff person syndrome (SPS) treated with autologous hematopoietic stem cell transplant (aHSCT). METHODS: This was a multicenter collaboration for the treatment of a single patient who underwent aHSCT as part of a clinical trial (NCT00716066). To objectively assess the response to transplantation, several clinical outcome measures were evaluated pretransplant and up to 18 months post-transplant, including modified Rankin Score (mRS), stiffness index, Hauser Ambulation Score (HAS), hypersensitivity index, timed 25-foot walk, and Montreal Cognitive Assessment. RESULTS: After transplant, the patient achieved sustained clinical improvement evidenced across various clinical scales, including mRS, stiffness index, HAS, and 25-foot walk time. DISCUSSION: aHSCT represents a promising treatment option for SPS, including for GlyR-positive patients. In addition, this case represents the need to validate and standardize best clinical outcome measures for patients with SPS. CLASSIFICATION OF EVIDENCE: Class IV; this is a single observational study without controls.

Prevalence, Clinical Profiles, and Prognosis of Stiff-Person Syndrome in a Japanese Nationwide Survey.

BACKGROUND AND OBJECTIVES: To elucidate current epidemiologic, clinical, and immunologic profiles and treatments of stiff-person syndrome (SPS) in Japan. METHODS: A nationwide mail survey was conducted using an established method. Data processing sheets were sent to randomly selected departments of internal medicine, neurology, pediatrics, psychiatry, and neurosurgery in hospitals and clinics throughout Japan to identify patients with SPS who were seen between January 2015 and December 2017. RESULTS: Thirty cases were identified as glutamic acid decarboxylase 65 (GAD65)-positive SPS cases on the basis of detailed clinical data of 55 cases. Four patients had α1 subunit of glycine receptor (GlyR) antibodies, and 1 patient had both GAD65 and GlyR antibodies. The total estimated number of patients with GAD65-positive SPS was 140, and the estimated prevalence was 0.11 per 100,000 population. The median age at onset was 51 years (range, 26-83 years), and 23 (76%) were female. Of these, 70% had classic SPS, and 30% had stiff-limb syndrome. The median time from symptom onset to diagnosis was significantly longer in the high-titer GAD65 antibody group than in the low-titer group (13 months vs 2.5 months, p = 0.01). The median modified Rankin Scale (mRS) at baseline was 4, and the median mRS at the last follow-up was 2. Among the 29 GAD65-positive patients with ≥1 year follow-up, 7 received only symptomatic treatment, 9 underwent immunotherapy without long-term immunotherapy, and 13 received long-term immunotherapy such as oral prednisolone. The coexistence of type 1 diabetes mellitus and the lack of long-term immunotherapy were independent risk factors for poor outcome (mRS ≥3) in the GAD65-positive patients (odds ratio, 15.0; 95% CI 2.6-131.6; p = 0.001; odds ratio, 19.8; 95% CI 3.2-191.5; p = 0.001, respectively). DISCUSSION: This study provides the current epidemiologic and clinical status of SPS in Japan. The symptom onset to the diagnosis of SPS was longer in patients with high-titer GAD65 antibodies than in those with low-titer GAD65 antibodies. The outcome of patients with SPS was generally favorable, but more aggressive immunotherapies are necessary for GAD65-positive patients with SPS.

[Stiff-Person Syndrome].

Stiff-person syndrome (SPS) is a rare autoimmune neurological disorder characterized by progressive axial muscle stiffness, central nervous system hyper-excitability, and painful stimulus-sensitive muscle spasms. SPS is classified into classic SPS and SPS variants, including stiff-limb syndrome (SLS) and progressive encephalomyelitis with rigidity and myoclonus (PERM), based on clinical presentation. SPS responds to immunotherapy, and several autoantigens have been identified. Most patients with SPS have high-titers of antibodies against glutamic acid decarboxylase (GAD), the rate-limiting enzyme for the synthesis of γ-aminobutyric acid (GABA), and up to 15% of the patients have antibodies against the glycine receptor α-subunit.

Therapies in Stiff-Person Syndrome: Advances and Future Prospects Based on Disease Pathophysiology.

Among the glutamic acid decarboxylase (GAD)-antibody-spectrum disorders, the most common phenotypic subset is the stiff-person syndrome (SPS), caused by impaired GABAergic inhibitory neurotransmission and autoimmunity characterized by very high titers of GAD antibodies and increased GAD-IgG intrathecal synthesis. If not properly treated or untreated because of delayed diagnosis, SPS progresses leading to disability; it is therefore fundamental to apply the best therapeutic schemes from the outset. This article is focused on the rationale of specific therapeutic strategies based on the SPS pathophysiology targeting both the impaired reciprocal GABAergic inhibition to symptomatically improve the main clinical manifestations of stiffness in the truncal and proximal limb muscles, gait dysfunction, and episodic painful muscle spasms and the autoimmunity to enhance improvement and slow down disease progression. A practical, step-by-step therapeutic approach is provided, highlighting the importance of combination therapies with the preferred gamma-aminobutyric acid-enhancing antispasmodic drugs, such as baclofen, tizanidine, benzodiazepines, and gabapentin, that provide the first-line symptomatic therapy, while detailing the application of current immunotherapies with intravenous immunoglobulin (IVIg) plasmapheresis, and rituximab. The pitfalls and concerns of long-term therapies in different age groups, including children, women planning pregnancy, and especially the elderly considering their comorbidities are emphasized, also highlighting the challenges in distinguishing the conditioning effects or expectations of chronically applied therapies from objective meaningful clinical benefits. Finally, the need for future targeted immunotherapeutic options based on disease immunopathogenesis and the biologic basis of autoimmune hyperexcitability are discussed, pointing out the unique challenges in the design of future controlled clinical trials especially in quantifying the extend and severity of stiffness, episodic or startle-triggered muscle spasms, task-specific phobias, and excitability.

Glutamic acid decarboxylase antibody-associated neurological syndromes: Clinical and antibody characteristics and therapy response.

BACKGROUND: Antibodies against glutamic acid decarboxylase (GAD-abs) at high serum levels are associated with diverse autoimmune neurological syndromes (AINS), including cerebellar ataxia, epilepsy, limbic encephalitis and stiff-person syndrome. The impact of low serum GAD-ab levels in patients with suspected AINS remains controversial. Specific intrathecal GAD-ab synthesis may serve as a marker for GAD-ab-associated nervous system autoimmunity. We present characteristics of a multicentric patient cohort with suspected AINS associated with GAD antibodies (SAINS-GAD+) and explore the relevance of serum GAD-ab levels and intrathecal GAD-ab synthesis. METHODS: All patients with SAINS-GAD+ included in the registry of the German Network for Research on Autoimmune Encephalitis (GENERATE) from 2011 to 2019 were analyzed. High serum GAD-ab levels were defined as RIA>2000 U/mL, ELISA>1000 U/mL, or as a positive staining pattern on cell-based assays. RESULTS: One-hundred-one patients were analyzed. In descending order they presented with epilepsy/limbic encephalitis (39%), cerebellar ataxia (28%), stiff person syndrome (22%), and overlap syndrome (12%). Immunotherapy was administered in 89% of cases with improvements in 46%. 35% of SAINS-GAD+ patients had low GAD-ab serum levels. Notably, unmatched oligoclonal bands in CSF but not in serum were more frequent in patients with low GAD-ab serum levels. GAD-ab-levels (high/low) and intrathecal GAD-ab synthesis (present or not) did not impact clinical characteristics and outcome. CONCLUSIONS: Overall, immunotherapy in SAINS-GAD+ was moderately effective. Serum GAD-ab levels and the absence or presence of intrathecal GAD-ab synthesis did not predict clinical characteristics or outcomes in SAINS-GAD+. The detection of unmatched oligoclonal bands might outweigh low GAD-ab serum levels.

Stiff person syndrome spectrum disorders; more than meets the eye.

Stiff person syndrome spectrum disorders (SPSD) are a group of rare neuroimmunological disorders that often include painful spasms and rigidity. However, patients have highly heterogeneous signs and symptoms which may reflect different mechanistic disease processes. Understanding subsets of patients based on clinical phenotype may be important for prognosis and guiding treatment. The goal of this review is to provide updates on SPSD and its expanding clinical spectrum, prognostic markers, and treatment considerations. Further, we describe the current understanding in immunopathogenesis and highlight gaps in our knowledge appropriate for future research directions. Examples of revised diagnostic criteria for SPSD based on phenotype are also presented.

[Stiff-Person Syndrome].

Stiff-person syndrome (SPS) is a neurological disorder characterized by fluctuating muscle rigidity and painful spasms that occur spontaneously or are triggered by diverse stimuli. Partial or segmental forms of the disorder, such as stiff-limb syndrome (SLS) and the more severe disease called progressive encephalomyelitis with rigidity and myoclonus (PERM), are usually considered within the spectrum of SPS. SPS responds to immunotherapies, and several autoantigens have been identified. Most patients with SPS have high titers of antibodies against glutamic acid decarboxylase (GAD), the enzyme that limits the rate of the synthesis of γ-aminobutyric acid (GABA), and up to 15% have antibodies against the glycine receptor α-subunit.

Use of subcutaneous immunoglobulin in stiff person syndrome: Case series.

INTRODUCTION: Intravenous immunoglobulin (IVIG) has been shown to be effective for the treatment of stiff person syndrome (SPS). However, some patients might not tolerate it. We report the tolerability profile of subcutaneous immunoglobulin (SCIg) in patients with SPS who did not tolerate IVIG. To our knowledge, the use of SCIg in SPS has not been reported before in a case series. PATIENT CONCERNS: The five patients included in this case series presented with various combinations of symptoms of spasms, axial and limb stiffness, and exaggerated responses to outside stimuli. These symptoms often lead to gait and functional impairment. DIAGNOSIS: Patients were diagnosed with classic SPS as they met the clinical criteria, which require the presence of spasms, axial rigidity, and hyperexcitability. INTERVENTIONS: Subcutaneous immunoglobulin infusion. OUTCOMES: Five patients were identified that were treated with SCIg. Three tested positive for serum anti-glutamic acid decarboxylase 65 antibodies prior to any treatment. The mean age at SCIg initiation was 33 years (range: 22-47). The mean duration of SPS prior to SCIg initiation was 5.9 years (range: 2.5-7). All patients used IVIG for at least two months (up to 18 months) but switched to SCIg due to IVIG side effects. Duration of SCIg use ranged from 4 months to 6 years (mean, 19.2 months). Upon switching to SCIg, the SPS symptoms remained stable. SCIg was well-tolerated in most as only one patient discontinued SCIg due to side effects. CONCLUSION: This case series highlights that SCIg could be a treatment option for patients with SPS, especially when IVIG is not feasible. Injection site reactions might be a limiting factor in some patients treated with SCIg. Prospective controlled studies are needed to confirm SCIg treatment durability and efficacy.

Ocular Motor and Vestibular Characteristics of Antiglutamic Acid Decarboxylase-Associated Neurologic Disorders.

BACKGROUND: Antiglutamic acid decarboxylase (GAD)-associated neurologic disorders are rare, with varied presentations, including stiff-person syndrome (SPS) and cerebellar ataxia (CA). Vestibular and ocular motor (VOM) dysfunction can be the main presentation in a subset of patients. METHODS: Retrospective review of the Johns Hopkins Hospital medical records from 1997 to 2018 identified a total of 22 patients with a diagnosis of anti-GAD-associated SPS or CA who had detailed VOM assessments. Eight had prominent VOM dysfunction at the initial symptom onset and were referred to neurology from ophthalmology or otolaryngology ("early dominant"). Fourteen patients had VOM dysfunction that was not their dominant presentation and were referred later in their disease course from neurology to neuro-ophthalmology ("nondominant"). We reviewed clinical history, immunological profiles, and VOM findings, including available video-oculography. RESULTS: In the 8 patients with early dominant VOM dysfunction, the average age of symptom onset was 53 years, and 5 were men. The most common symptom was dizziness, followed by diplopia. Seven had features of CA, and 4 had additional features of SPS. None had a structural lesion on brain MRI accounting for their symptoms. The most common VOM abnormalities were downbeating and gaze-evoked nystagmus and saccadic pursuit. All received immune therapy and most received symptomatic therapy. Most experienced improvement in clinical outcome measures (modified Rankin scale and/or timed 25-foot walk test) or VOM function. By contrast, in the 14 patients in whom VOM dysfunction was nondominant, most had an SPS phenotype and were women. VOM abnormalities, when present, were more subtle, although mostly still consistent with cerebellar and/or brainstem dysfunction. CONCLUSIONS: Individuals with anti-GAD-associated neurologic disorders may present with prominent VOM abnormalities at the initial symptom onset that localize to the cerebellum and/or brainstem. In our cohort, immune and symptomatic therapies improved clinical outcomes and symptomatology.

Autologous haematopoietic stem cell transplantation for refractory stiff-person syndrome: the UK experience.

Stiff Person Syndrome (SPS) is a rare immune-mediated disabling neurological disorder characterised by muscle spasms and high GAD antibodies. There are only a few case reports of autologous haematopoietic stem cell transplantation (auto-HSCT) as a treatment for SPS. OBJECTIVE: To describe the UK experience of treating refractory SPS with auto-HSCT. METHODS: Between 2015 and 2019, 10 patients with SPS were referred to our institution for consideration of auto-HSCT. Eight patients were deemed suitable for autograft and four were treated. Of the treated patients, three had classical SPS and one had the progressive encephalomyelitis with rigidity and myoclonus variant. All patients were significantly disabled and had failed conventional immunosuppressive therapy. Patients were mobilised with Cyclophosphamide (Cy) 2 g/m2 + G-CSF and conditioned with Cy 200 mg/kg + ATG followed by auto-HSCT. RESULTS: Despite their significantly reduced performance status, all patients tolerated the procedure with no unexpected toxicities. Following autograft, all patients improved symptomatically and stopped all forms of immunosuppressive therapies. Two patients were able to ambulate independently from being wheelchair dependent. One patient's walking distance improved from 300 meters to 5 miles and one patient's ambulation improved from being confined to a wheelchair to be able to walk with a frame. Two patients became seronegative for anti-GAD antibodies and normalised their neurophysiological abnormalities. CONCLUSIONS: Auto-HSCT is an intensive but well tolerated and effective treatment option for patients with SPS refractory to conventional immunotherapy. Further work is warranted to optimise patient selection and establish the efficacy, long-term safety, and cost-effectiveness of this treatment.

The effect of clinical pilates-based physiotherapy program for a Stiff Person Syndrome patient: a case report.

The aim of the present report is to show the effects of a clinical pilates-based physiotherapy training program on physical functioning, including balance ability, flexibility, muscle strength, and pain severity in a case with Stiff Person Syndrome (SPS). A 43-year-old female with a 3-year history of SPS participated in the study. Clinical pilates training exercises were performed two times per week during 8 weeks. Static balance was evaluated with One Leg Stance Test and Tandem Stance Test, dynamic balance with Functional Reach Test and lower extremity strength and endurance measured by 30-s Chair Stand Test. Berg Balance Scale was used to assess balance and fall risk, and Timed Up and Go Test was used to assess functional mobility. Pain evaluation was done by Pain Quality Assessment Scale. Flexibility was measured with tape measure, range of motion with goniometer and muscle strength with manual muscle test. Among the balance and functional mobility tests, progress has been observed in all tests, except for 30-s Chair Stand test. Improvements have been observed in patient's range of motion, flexibility, strength, pain and balance parameters. Clinical pilates-based physiotherapy program had positive effects on many physical and functional parameters of the patient and can be used as a safe exercise method in physiotherapy rehabilitation of SPS.

Autologous Hematopoietic Stem Cell Transplantation for Stiff-Person Spectrum Disorder: A Clinical Trial.

OBJECTIVE: To test the hypothesis that autologous nonmyeloablative hematopoietic stem cell transplantation (HSCT) is safe and shows efficacy in the treatment of stiff-person spectrum disorder (SPSD). METHODS: Twenty-three participants were treated in a prospective open-label cohort study of safety and efficacy. After stem cell mobilization with cyclophosphamide (2 g/m2) and filgrastim (5-10 µg/kg/d), participants were treated with cyclophosphamide (200 mg/kg) divided as 50 mg/kg IV on day -5 to day -2; rabbit anti-thymocyte globulin (thymoglobulin) given intravenously at 0.5 mg/kg on day -5, 1 mg/kg on days -4 and -3, and 1.5 mg/kg on days -2, and -1 (total dose 5.5 mg/kg); and rituximab 500 mg IV on days -6 and +1. Unselected peripheral blood stem cells were infused on day 0. Safety was assessed by survival and National Cancer Institute common toxicity criteria for adverse events during HSCT. Outcome was assessed by ≥50% decrease or discontinuation of antispasmodic drugs and by quality of life instruments. RESULTS: There was no treatment-related mortality. One participant died 1 year after transplantation of disease progression. Of the 74% of participants who responded, 47% have stayed in remission for a mean of 3.5 years; 26% did not respond. Compared to nonresponders, responders were more likely to have pretransplantation intermittent muscle spasms (16 of 17 vs 0 of 6), normal reflexes (12 of 17 vs 0 of 6), and positive CSF anti-glutamic acid decarboxylase serology (12 of 14 vs 2 of 6). Compared to responders, nonresponders were more likely to have lead pipe rigidity (4 of 6 vs 0 of 17) and EMG-documented simultaneous contraction of agonist/antagonist limb muscles (4 of 6 vs 1 of 17). Pre-HSCT use of prescription serotonin selective receptor inhibitor (SSRI) or serotonin and norepinephrine reuptake inhibitor (SNRI) was more common in those who relapsed or never responded (9 of 12) compared to those responders who never relapsed (0 of 11). CONCLUSION: In this cohort, HSCT was safe, but the beneficial effect of HSCT was variable and confined predominately to participants with episodic spasms and normal tendon reflexes without simultaneous cocontraction of limb agonist/antagonist muscles who were not taking SSRI or SNRI antidepressants. CLASSIFICATION OF EVIDENCE: This study provides Class IV evidence that, for a subset of people with SPSD, autologous nonmyeloablative HSCT improves outcomes. CLINICALTRIALSGOV IDENTIFIER: NCT02282514.

Defining the Expanding Clinical Spectrum of Pediatric-Onset Stiff Person Syndrome.

BACKGROUND: We aimed to characterize the spectrum of clinical features and examination findings in pediatric-onset stiff person syndrome. METHODS: Medical records were reviewed for all patients treated for stiff person syndrome with symptom onset in childhood at a tertiary medical center between March 2001 and February 2019. RESULTS: Of the 15 individuals who met inclusion criteria, 11 (73%) were female and 13 (87%) were Caucasian. Median age at symptom onset was 14.8 years (range 8.4 to 16.9), and median latency from symptom onset to diagnosis was 6.2 years (range 0.4 to 15.0). Nine individuals (60%) were not diagnosed until adulthood. The most common presenting features were painful spasms (n = 12, 80%), hyper-reflexia (n = 11, 73%), axial rigidity (n = =9, 60%), lower extremity rigidity or spasticity (n = 8, 53%), gait abnormalities (n = 6, 40%), and hyperlordosis (n = 6, 40%). Other noted features included anxiety (n = 5, 33%), dysautonomia (n = 3, 20%), and cranial neuropathies (n = 3, 20%). Personal (n = 9, 60%) and family history (n = 9, 60%) of autoimmune conditions was common. Serum antiglutamate decarboxylase 65 antibodies were found in 13 individuals (87%). Nearly all individuals received immunotherapy (n = 14, 93%), symptomatic medications (n = 15, 100%), and nonpharmacologic therapies (n = 14, 93%). However, most had persistent physical limitations, particularly impaired walking (n = 7, 47%) and inability to carry out previous activities (n = 14, 93%). CONCLUSIONS: There is a wide spectrum of typical and less common features seen in individuals with pediatric-onset stiff person syndrome. Despite symptom onset in childhood, diagnosis is often delayed until adulthood, at which point disability accrual is frequently seen. Early recognition is vital to address symptoms and may potentially limit future disability.