Abstract
Stiff Person Syndrome (SPS) is a rare autoimmune neurological disorder linked to anti-GAD antibodies, marked by muscle rigidity, spasms, and heightened sensitivity to stimuli, predominantly affecting axial muscles. Managing SPS during pregnancy is complex and necessitates a multidisciplinary approach. This case report details the management of a 32-year-old pregnant woman with SPS and type 1 diabetes mellitus. Diagnosed 10 years prior to pregnancy, her SPS was managed with intravenous immunoglobulin, diazepam, and baclofen. During pregnancy, adjustments were made to minimise potential risks; diazepam was replaced with clonazepam near delivery to support breastfeeding, and IVIG dosing was modified based on symptoms. Her type 1 diabetes remained well controlled with an insulin pump. Delivery planning addressed risks of SPS spasms, shoulder dystocia, and caesarean recovery. This case highlights the importance of individualised care and collaboration among specialists in managing pregnancy with SPS.
Introduction
Stiff Person Syndrome (SPS) is a rare autoimmune neurological disorder characterised by muscle rigidity and spasms, primarily affecting axial muscles. Heightened sensitivity to stimuli such as noise, touch, or stress can trigger debilitating spasms. 1 Its estimated prevalence is approximately 1–2 cases per million. 2 SPS is associated with autoantibodies against glutamic acid decarboxylase (GAD), an enzyme crucial in GABAergic neurotransmission. The resulting deficiency in gamma-aminobutyric acid (GABA), an inhibitory neurotransmitter, contributes to abnormal muscle rigidity and spasms. SPS frequently coexists with type 1 diabetes (T1D) due to shared autoimmune mechanisms, with GAD autoantibodies attacking pancreatic beta cells in T1D and the central nervous system in SPS. 3 About one in three individuals with SPS also have T1D. 4
This case report discusses the multidisciplinary management of a pregnant woman with SPS and T1D, focusing on her pregnancy, treatment adjustments, and delivery planning.
Case report
A 32-year-old woman with a history of T1D and SPS, diagnosed 11 years prior, presented for obstetric care at 13 weeks’ gestation. Her SPS, associated with anti-GAD antibodies, had been managed with intravenous immunoglobulin (IVIG) therapy since diagnosis. Initially, the woman experienced freezing episodes, which progressed to frequent severe muscle spasms and falls triggered by loud noises. Following magnetic resonance imaging (MRI), electromyography (EMG), and lumbar puncture, SPS was diagnosed, leading to IVIG initiation.
Her T1D was well-controlled with continuous subcutaneous insulin infusion (CSII), and she maintained excellent glucose control throughout pregnancy. During pregnancy, treatment adjustments were made. A dose of IVIG was omitted in the second trimester due to symptomatic improvement, but this was not sustained. During pregnancy, diazepam and baclofen were reduced, aiming for the minimal effective dose. Near term, diazepam was switched to clonazepam for its potentially more favourable safety profile in breastfeeding.
Obstetric consultations focused on delivery planning. Delivery planning involved discussions on vaginal versus caesarean section (CS), considering factors such as unpredictable muscle spasms, risk of shoulder dystocia from T1D, and potential recovery challenges. After thorough counselling, the patient wanted to minimise risks of intrapartum complications so opted for an elective CS. This was performed at 37 + 3 weeks due to T1D and her absolute wish to avoid labour. The CS was uncomplicated.
A healthy female infant was delivered, weighing 3.78 kg with no withdrawal symptoms or feeding difficulties. Intraoperatively, her CSII basal insulin rate was reduced by 25% to prevent hypoglycaemia. Clonazepam doses were increased postpartum due to exacerbation of SPS symptoms, achieving satisfactory symptom control. At two months postpartum, her therapy was adjusted back to diazepam and baclofen, with ongoing IVIG therapy and neurology follow-up.
Discussion
Effects of SPS on pregnancy
SPS can significantly affect pregnancy, with muscle rigidity and spasms increasing the risk of falls and affecting daily function. Stress and hormonal fluctuations may exacerbate symptoms, with some cases showing symptom stabilisation or improvement, while others indicate continued or worsening symptoms with the possibility of postnatal flare, increasing the risk of dropping the baby and compromising neonatal safety.
Effects of pregnancy on SPS
Pregnancy-related immunomodulation may temporarily improve SPS symptoms, similar to other immune-mediated conditions such as multiple sclerosis. This suggests that the immunosuppressive state of pregnancy may reduce autoimmune attacks on GABAergic pathways.5,6 However, postpartum reversal of these changes can lead to symptom exacerbation. Due to limited understanding of SPS in pregnancy, individualised treatment planning is crucial, with baclofen, benzodiazepines, and IVIG being potential therapeutic options during pregnancy if needed. Additionally, delivery planning and postpartum medication review are essential, given the high risk of symptom worsening. A case series of nine pregnant women with SPS reported stabilisation or improvement in five cases, accompanied by reduced antispasmodic medication use, and all nine delivered healthy infants. 7
Treatment choices in pregnancy
Early initiation of IVIG in pregnancy is recommended to improve function and minimise fetal exposure to GABA-enhancing medications. Medication safety must be carefully considered.
Benzodiazepines, such as diazepam and clonazepam, are commonly used for symptom relief, but their use in pregnancy is associated with potential risks, including neonatal withdrawal syndrome and sedation. However, their benefits in controlling debilitating muscle spasms may justify cautious use at the lowest effective dose.
Baclofen, a GABA-B receptor agonist, is another key treatment for SPS, and while data on its use in pregnancy is limited, case reports suggest it can be used with caution. Abrupt discontinuation poses a significant risk of withdrawal symptoms, including seizures, which can be harmful to both the mother and fetus.
IVIG frequently used in autoimmune neurological conditions, is generally considered safe during pregnancy and is often used to manage other responsive autoimmune conditions in pregnancy.
On the other hand, medications such as pregabalin, often used for neuropathic pain, have inconclusive evidence on their safety and should be reserved for severe cases. Given the complexities of medication safety in pregnancy, a multidisciplinary approach, involving neurology and maternal-fetal medicine, is critical for optimising maternal health while minimising fetal risks. 8
Mode of delivery
Caesarean delivery is not mandatory for SPS patients, and vaginal delivery is possible with appropriate support, including positioning modifications and epidural anaesthesia for pain management. The choice of delivery mode should be individualised based on disease severity, risk of severe muscle spasms, obstetric factors, and patient preference.
Concurrent T1D and SPS management
Concurrent T1D and SPS management involves addressing comorbid autoimmune conditions with coordinated care, requiring close coordination between obstetric, neurology, and endocrinology teams. Patients with SPS spectrum disorders may present with classical SPS alongside additional features such as cognitive impairment, brainstem signs, cerebellar ataxia, seizures, or myoclonus. Management of these symptoms requires further coordinated care with neurology and physiotherapist. 4
Insulin requirements fluctuate throughout pregnancy, and continuous glucose monitoring (CGM) alongside CSII optimises glycaemic control, reducing maternal and fetal complications. Peripartum insulin adjustments are crucial, with CSII basal rates modified during labour or surgery to prevent hypoglycaemia.
Breastfeeding considerations
Breastfeeding is encouraged, though medication safety must be evaluated. Benzodiazepines transfer into breast milk and may cause neonatal sedation or feeding difficulties, necessitating the lowest effective doses. Diazepam was later switched to clonazepam near term, which has possible less transfer into breastmilk. Baclofen appears in low concentrations in breast milk but may impact neonatal tone and feeding. Close monitoring of neonatal responses to maternal medications is advised however, the need for these medications does not preclude breastfeeding. IVIG does not pose significant concerns for breastfeeding and can be continued postpartum.
Conclusion
This case highlights the critical role of a multidisciplinary approach, involving the obstetric, obstetric medicine, neurology, anaesthetic, midwifery and diabetes teams, to achieve favourable outcomes for both mother and child. Treatment should be tailored to balance symptom control with fetal safety, considering adjustments to medication regimens and delivery planning. While pregnancy may lead to temporary symptom improvement in some cases, the postpartum period is a critical time for monitoring, intervention and adherence to baby safety advice due to the high risk of symptom exacerbation. Multidisciplinary team involvement is critical for both ongoing management and delivery planning for such cases.
Footnotes
Acknowledgements
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Ethical approval
Imperial College Healthcare NHS Trust does not require ethical approval for reporting individual cases or case series.
Informed consent
Written informed consent was obtained from the patient for their anonymised information to be published in this article.
Author contributors
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Funding
The authors received no financial support for the research, authorship, and/or publication of this article.
Declaration of conflicting interests
The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.
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