
==== Front
Ann Indian Acad Neurol
Ann Indian Acad Neurol
AIAN
Ann Indian Acad Neurol
Annals of Indian Academy of Neurology
0972-2327
1998-3549
Wolters Kluwer - Medknow India

39150463
AIAN-27-419
10.4103/aian.aian_92_24
Case Report
Expanding the Understanding of Stiff-Person Syndrome: Insights from 17 Cases in India
Jain Rajendra S.
Pemawat Ashish
Sharma Pankajkumar
Nehra Kuldeep
Department of Neurology, University S.M.S Medical College and Hospital, Jaipur, Rajasthan, India
Address for correspondence: Dr. Rajendra S. Jain, Department of Neurology, University S.M.S Medical College, Jaipur, Rajasthan, India. E-mail: drrsjain@yahoo.com
Jul-Aug 2024
16 8 2024
27 4 419425
06 2 2024
28 5 2024
10 6 2024
Copyright: © 2024 Annals of Indian Academy of Neurology
2024
https://creativecommons.org/licenses/by-nc-sa/4.0/ This is an open access journal, and articles are distributed under the terms of the Creative Commons Attribution-NonCommercial-ShareAlike 4.0 License, which allows others to remix, tweak, and build upon the work non-commercially, as long as appropriate credit is given and the new creations are licensed under the identical terms.
Stiff-person syndrome (SPS) is a rare and complex neurologic disorder characterized by progressive muscle stiffness, painful spasms, and gait difficulties. In this report, we describe a case of SPS who presented with a relapse while on maintenance immunosuppressive treatment. In addition, we review the literature of 16 previously reported cases of SPS from India, highlighting the diverse clinical features, comorbidities, treatment response, and relapse. The occurrence of paraneoplastic SPS emphasizes the need for early recognition and diagnosis.

Anti-GAD antibody
paraneoplastic SPS
PERM
stiff person syndrome
stiff limb syndrome
==== Body
pmcINTRODUCTION

“Stiff-man syndrome” was first described in 1956 by Moersch and Woltman.[1] They reported the symptoms of a 49-year-old man, including progressive stiffness in the neck, shoulders, upper back, muscle spasms, and walking difficulties. Asher first proposed the gender-neutral term “Stiff Person Syndrome” (SPS) in 1958[2] which gained traction after Blum and Jankovic reported that about 20 of the 84 cases from 1967 to 1991 were females.[3] Core features of fluctuating muscle stiffness, superimposed spasms, and exaggerated startle responses characterize SPS. An immunologic origin was suspected due to the frequent co-occurrence of diabetes mellitus (DM) and other autoimmune conditions in SPS patients.[4] In 1988, the presence of glutamic acid decarboxylase (GAD) antibodies (Ab) was documented in association with SPS.[5] These antibodies were found to inhibit GAD activity and gamma-aminobutyric acid (GABA) synthesis in vitro.[6] In this article, we report a case of SPS who presented with a relapse during immunotherapy. In addition, we reviewed the literature of 16 previously reported cases of stiff person syndrome from India, providing insights into the clinical profile, treatment, and outcomes of this rare disorder.

CASE REPORT

A 58-year-old female, diagnosed case of SPS for 7 years, presented to us in a relapse state while being on a combination of oral prednisolone and mycophenolate mofetil for the past four years. Her relapse was characterized by increasing trunk and lower limb stiffness, painful spasms, and exaggerated startle response over the past 3 months. She was also on a daily dose of thyroxine (50 µg) for hypothyroidism. Serum anti-GAD and anti-thyroid peroxidase (TPO) Ab were positive. A combination of medications including diazepam, baclofen, and gabapentin was initiated to alleviate stiffness and spasms. Intravenous immunoglobulin (IVIG) was administered at a dosage of 2gm/kg divided over 5 days, followed by rituximab infusion (1000 mg each at day 0, 14) for long-term immunosuppression. Her pre-treatment modified Rankin Scale (mRS) score was 5. At her three-month follow-up, she showed notable improvement in stiffness and reported that her painful spasms had fully resolved, with her mRS score now reduced to 3.

DISCUSSION

This article provides a comprehensive overview of the clinical spectrum, treatment, and outcomes of SPS cases reported from India, including the current case [Tables 1 and 2]. The clinical classification of SPS consists of classic SPS, partial SPS variants, and progressive encephalomyelitis with rigidity and myoclonus (PERM).[23] Classic SPS is the most prevalent form, affecting 70-80% of SPS patients.[24] Diagnosis of SPS is based on clinical features of stiffness in the limb and axial muscles, prominent in the abdomen and thoracolumbar region, painful spasms precipitated by unexpected tactile and auditory stimuli, electrophysiological finding of continuous motor unit activity in agonist and antagonist muscles, positive serology for anti-GAD65 or anti-amphiphysin autoantibodies, absence of other neurological impairments that could support an alternative diagnosis, and clinical response to therapy with benzodiazepines.

Table 1 Summary of SPS case reports from India

Study/year	Age/gender	Diagnosis	Duration of illness	Clinical profile	Neurologic examination	Other neurologic conditions	Other autoimmune/systemic illness/malignancy	Investigations	Treatment and outcome	
Markandeyulu et al./2001[7]	11/M	SPS	5 years	Upper, lower limb, and trunk stiffness
Painful spasm
Abnormal posturing
Stimulus sensitivity	Brisk reflexes, clumsy wide-based gait, exaggerated lumbar lordosis	_	_	EMG: CMUA	Diazepam
Improvement	
Saravanan et al./2002[8]	43/F	SPS	15 years	Lower limb and trunk stiffness
Painful spasm	B/L ptosis, EOM restriction, grip weak		MG	EMG: CMUA	IV diazepam, IV Prostigmin	
Misra et al./2009[9]	42/M	SPS	3 years	Stiffness
Painful spasm
Abnormal posturing
Stimulus sensitivity, vomiting, hiccups	Hypertonia, diminished ankle reflex, lower limb hyperesthesia, rest normal	_	_	CSF anti-GAD Ab (-)	Diazepam
Improvement	
Agarwal et al./2010[10]	55/F	SLS	2 months	Right leg stiffness
Painful spasm
Abnormal posturing
Stimulus sensitivity	Hypertonia (right lower limb)	_	Breast carcinoma (infiltrative ductal carcinoma)	Serum anti-GAD Ab (+)
EMG-CMUA	Baclofen, diazepam, oral prednisolone, surgery, and CT for breast Ca
Relapse on tapering steroids
Improvement	
Khade et al./2012[11]	40/F	SPS	2 years	Stiffness
Painful spasm
Abnormal posturing
Stimulus sensitivity	Hypertonia	_	IDDM	Serum anti-GAD Ab (+)
Serum anti-TPO Ab (+)
EMG: CMUA	Diazepam, baclofen, IVIg
Relapse: first on diazepam, second after 1.5 years of IVIg
Improvement	
Saigal et al./2015[12]	38/M	SPS	3 years	Trunk, lower limb stiffness
Painful spasm
Abnormal posturing
Stimulus sensitivity	Hypertonia, Lower Limb reflex brisk, robotic gait, Exaggerated lumbar lordosis	_	IDDM	Serum anti-GAD Ab (+)
EMG-CMUA	Clonazepam, baclofen
Improvement	
Chakravarthi et al./2015[13]	50/M	SPS	3 months	Trunk and lower limb stiffness
Painful spasm	Tonic deviation of eyes to left, EOM restriction to right, hypertonia, brisk reflexes, exaggerated cervicothoracic and lumbar lordosis	_	Thymoma type B3	Serum anti-GAD Ab
(-)
EMG: CMUA	IVIg, thymectomy
Improvement	
Chaudhari et al./2015[14]	36/F	SPS	3 years	Lower limb and trunk stiffness
Painful spasm	Hypertonia, antalgic gait	GTCS	Right neck of femur fracture	CSF and serum anti-GAD Ab (+)
EMG: CMUA	Midazolam infusion, intrathecal baclofen
Improvement	
Maramattom 2015[15]	64/M	SPS	5 months	Stiffness
Painful spasm	Hypertonia, exaggerated lumber lordosis	Status spasticus	DM, rhabdomyolysis	Serum anti-GAD Ab (+)	IV diazepam, IV vecuronium, mechanical ventilation, oral baclofen, oral gabapentin, IVIg
Improvement	
Sharma et al./2016[16]	30/F	SPS	1.5 months	Stiffness
Painful spasm	Cognitive impairment, slow saccades with broken pursuits, hypertonia, cerebellar signs, ataxic gait	Autoimmune limbic encephalitis, seizure (GTCS)	Type 1 DM	CSF and serum anti-GAD Ab (+)
EMG: CMUA
MRI-brain: B/L medial temporal hyperintensities	Baclofen, clobazam, levetiracetam, IVIg, azathioprine
Improvement	
Kumar et al./2016[17]	8/M	SPS	2 months	Stiffness
Painful spasm
Abnormal posturing
Stimulus sensitivity	Hypertonia, brisk reflexes, exaggerated lumbar lordosis	Myoclonic jerk	Myoglobin induced ATN	CSF anti-GAD Ab (+)	Clonazepam, valproate, MPS, IVIg, rituximab, oral prednisolone
Improvement	
Nene et al./2019[18]	58/F	SPS	1 month	Stiffness
Painful spasms, headache, vertigo	B/L gaze-evoked nystagmus, power 4/5, brisk reflexes, gait ataxia	_	Hiatal hernia, gastric ulcer	Serum anti-GAD Ab (+)	Diazepam, baclofen, IVIg, MMF, steroids
Improvement	
Shivaram et al./2021[19]	58/M	SPS	10 months	Lower limb stiffness
Painful spasm
Stimulus sensitivity	Hypertonia	_	_	Serum anti-GAD Ab (+)
EMG-CMUA	Symptomatic medications and immunotherapy
Improvement	
Ray et al./2022[20]	24/M	SPS	1 year	Lower > upper limb and trunk stiffness	Hypertonia, weakness of small muscles of the left hand, brisk reflexes, plantar extensor, exaggerated lumbar lordosis, left hand wasting, polyminimyoclonus, fasciculations	Monomelic brachial amyotrophy	_	CSF anti-GAD Ab (+)
EMG: fasciculations and polyphasic MUAP in left abductor digiti minimi
MRI spine - lower cervical cord atrophy	Clonazepam, gabapentin, IVIg
Improvement	
Kamaleshwaran et al./2023[21]	64/F	SPS	1 month	Stiffness		_	DM, HTN	Serum anti-GAD Ab (+)	Rituximab
Improvement	
Mandal et al./2023[22]	49/M	SPS	1 month	Right upper and lower limb stiffness	Multidirectional gaze-evoked nystagmus, hypertonia, spastic and ataxic gait, cerebellar signs	_	DM	CSF and serum anti-GAD Ab (+)
EMG paraspinal muscles-CMUA	Diazepam, MPS, plasmapheresis, rituximab
Improvement	
Our case	58/F	SPS	7 years	Trunk stiffness
Painful spasm
Stimulus sensitivity	Hypertonia, exaggerated lumbar lordosis	_	Hypothyroidism	Serum anti-GAD Ab (+)
Serum anti-TPO Ab (+)	Diazepam, baclofen, gabapentin, IVIg, rituximab
Improvement	
Ab=antibodies, CSF=cerebrospinal fluid, CT=computed tomography, DM=diabetes mellitus, GAD=glutamic acid decarboxylase, HTN=hypertension, IV=intravenous, IVIg=intravenous immunoglobulin, MRI=magnetic resonance imaging, SPS=stiff-person syndrome, B/L=bilateral, IDDM=insulin dependent diabetes mellitus, ATN=acute tubular necrosis, MPS=methylprednisolone,

Table 2 Overview of demographic, clinical, investigation, treatment, and outcome details of SPS case reports

	No.	
Demographic details	
    Total cases analyzed
    Male
    Female
    Adult cases (>18 years)
    Pediatric cases (≥18 years)
    Mean age (years); range; [median (IQR)]	17
9
8
15
2
42.8; 8-64; [43 (25)]	
Diagnosis	
    SPS
    SLS	16 (94%)
1 (6%)	
Duration of illness
    Mean (months); range; [median (IQR)]	
29; 1-180; [10 (34.2)]	
Clinical profile	
    Symptoms
    Stiffness
    Painful spasm
    Abnormal posturing
    Stimulus sensitivity/exaggerated startle
    Cognitive impairment
    Seizure (GTCS)
    Myoclonus
    Ataxia	
17 (100%)
14 (82%)
7 (42%)
8 (48%)
1 (6%)
2 (12%)
1 (6%)
3 (18%)	
Oculomotor involvement
    Slow saccades with broken pursuit
    Gaze-evoked nystagmus
    Bilateral ptosis with EOM restriction
    Tonic eye deviation to left with EOM restriction to right
    Brachial monomelic amyotrophy	
1 (6%)
2 (12%)
1 (6%)
1 (6%)
1 (6%)	
Other autoimmune/systemic illnesses
    DM
    MG
    Hypothyroidism	
6 (36%)
1 (6%)
1 (6%)	
Malignancy
    Carcinoma breast
    Thymoma
    Orthopedic complication	
1 (6%)
1 (6%)
2 (12%)	
Anti-GAD antibody
    Positive
    Negative
    N/A	
13 (serum anti-GAD-12 [72%], CSF anti-GAD-4 [24%])
2 (12%)
2 (12%)	
Other autoantibodies
    Anti-TPO antibody
Neuroimaging findings
    Bilateral medial temporal hyperintensity
    Cervical cord atrophy	
2 (12%)

1 (6%)
1 (6%)	
EMG
    CMUA
    Fasciculations with polyphasic MUAP	
10 (60%)
1 (6%)	
Treatment	
 Symptomatic treatment
    Benzodiazepines
    Baclofen
    Levetiracetam
    Sodium valproate
    Vecuronium	
14 (82%)
8 (48%)
1 (6%)
1 (6%)
1 (6%)	
Mechanical ventilation Immunotherapy	1 (6%)
	
Steroid
    IVIg
    Rituximab
    Plasmapheresis
    Azathioprine
    MMF
    Surgery
Outcome
    Improvement
    With symptomatic alone
    With symptomatic plus immunotherapy
Relapse	5 (30%)
8 (48%)
4 (24%)
1 (6%)
1 (6%)
2 (12%)
2 (12%)

4 (24%)
12 (72%)
3 (18%)	
DM=diabetes mellitus, GAD=glutamic acid decarboxylase, IQR=interquartile range, IVIg=intravenous immunoglobulin, SPS=stiff-person syndrome, SLS=stiff leg syndrome, GTCS=generalised tonic-clonic seizure, MG=myasthenia gravis, EMG=electromyography, MMF=mycophenolate mofetil

In this SPS cohort, 16 out of 17 cases (94%) were diagnosed with SPS, while one case (6%) was classified as stiff limb syndrome. The median duration of illness was 10 months (mean 29 months). The median age of patients at the time of presentation was 43 years (mean 42.8, interquartile range 25). The female-to-male ratio was 1:125 (eight females and nine males). Pediatric cases (<18 years) comprised 12% of the total, while 88% of cases involved adults (≥18 years). A study by Mckeon et al.[23] included 99 patients, 67 of whom were female. The median age at symptom onset was 40 years, ranging from 5 to 70 years. Five patients experienced symptoms before the age of 18. Another study by Dalakas et al.[25] included 20 SPS patients (six men and 14 women) with an average onset age of 41.2 years. SPS is rare in pediatric cases, accounting for only 5% of total cases.[26] In the current SPS cohort, the most common symptoms were stiffness in all 17 patients and painful spasms in 82%. Abnormal posturing was seen in 42% of patients, and 48% experienced stimulus sensitivity and exaggerated startle response. These results align with previously published studies.[232527] Cranial nerve involvement was reported in five (30%) patients, manifesting as gaze-evoked nystagmus, slow saccade with broken pursuit, ptosis with extraocular movement (EOM) restriction, and tonic eye deviation. Gait ataxia occurred in 24% of cases. Extraocular abnormalities such as oscillopsia, opsoclonus, and nystagmus were reported previously,[28] and patients with the cerebellar variant of SPS presented with dysmetria, gait ataxia, and nystagmus superimposed on stiffness.[29] In the current SPS cohort, one case of SPS was associated with autoimmune limbic encephalitis and bilateral medial temporal hyperintensity, while another case presented with left upper limb weakness, fasciculations, polyphasic motor unit action potential (MUAP) in the left abductor digiti minimi, and cervical cord atrophy. Pittock et al.[30] reported varying neurologic manifestations in association with anti-GAD Ab, including cerebellar ataxia (63%), brainstem involvement (29%), seizures (27%), stiff-person phenomena (26%), extrapyramidal signs (16%), and myelopathy (8%). In the current SPS cohort, coexisting autoimmune disorders included DM in 36% of cases, myasthenia gravis in one case, and hypothyroidism in another. SPS may coexist with other autoimmune disorders, including DM type 1 (DM-1), autoimmune thyroid disease, pernicious anemia, celiac disease, and vitiligo.[31] McKeon et al.[23] reported DM-1 in 43% (34 of 79) and autoimmune thyroid disease in 35% (28 of 79) in their study. In a study by Sarva et al.,[27] eight patients had coexisting diabetes and another had autoimmune disease. Pittock et al.[30] reported in their study that one-third of the patients had DM-1, 53% had thyroid autoantibodies, and 16% had vitiligo. In the current SPS cohort, two cases (12%) were associated with malignancies including breast carcinoma and thymoma. In a study by McKeon et al.,[23] three cases (4%) involved carcinoma (thyroid, renal cell, and colon). Various case reports of SPS in association with Hodgkin and non-Hodgkin lymphomas, thymoma, and breast malignancy are documented in the literature.[24323334] In the current SPS cohort, anti-GAD Ab were present in 72% of patients and cerebrospinal fluid (CSF) anti-GAD Ab were found in 24%, including 18% of cases with positivity in both serum and CSF. Besides anti-GAD Ab, other antibodies [Table 3] have been associated with SPS.[273035]

Table 3 Clinical manifestations of SPS spectrum in association with various autoantibodies

Antibody	Clinical features	
Amphiphysin	Paraneoplastic SPSD (breast or small cell lung carcinoma), sensory ganglionopathy	
GAD	Endocrine or organ-specific autoimmunity (type 1 DM, thyroid disorders, pernicious anemia, vitiligo) ataxia, epilepsy, preceding episodes of brainstem/cerebellar dysfunction. Paraneoplastic SPSD (rare)	
Gephyrin	Paraneoplastic with mediastinal cancer, idiopathic autoimmune cases	
GABARAP	In conjunction with GAD antibodies	
GABAAR	Epilepsy, early age of onset (below 20 years), encephalitis with prominent epilepsy, sometimes with chorea, paraneoplastic SPS, more frequent in patients with autoimmune predisposition and other antibodies	
GlyR	Hyperekplexia, prominent brainstem involvement, better response to immunotherapy, CSF abnormalities in 50% of patients, paraneoplastic SPSD (in approximately 10% of cases)	
GlyT2	Hyperekplexia	
DPPX	Hyperekplexia, prominent cerebellar ataxia, trunk stiffness, somatosensory disturbances, cognitive decline, prominent gastrointestinal hyper/hypomobility, weight loss, dysautonomia (diaphoresis, cardiac arrhythmias, urinary symptoms), sleep disturbances. Paraneoplastic etiology in 7% of cases, good response to immunotherapy	
CSF=Cerebrospinal fluid, DM=Diabetes mellitus, GAD=Glutamic acid decarboxylase, SPS=Stiff-person syndrome, SPSD=stiff person spectrum disorder

GAD antibodies (Ab) are detected in 60%–80% of classical Stiff-Person Syndrome (SPS) cases.[23] GAD Ab also occurs in 0.4%–1.7% of healthy people and 5% of patients with other neurological disorders.[36] High GAD Ab levels are defined by Radioimmunoassay(RIA) value greater than 2000 U/mL, by an Enzyme-linked immunosorbent assay (ELISA) value greater than 1000 IU/mL or 20 nmol/L, or by strong positive labeling at low dilutions for immunohistochemistry.[37] Only patients with GAD-related neurological syndromes have GAD Ab detected in their CSF.[37] GAD serum Ab titers do not significantly vary among SPS, cerebellar ataxia, and limbic encephalitis, suggesting phenotype is influenced more by epitope specificity than Ab titers.[38] No correlation exists between Ab titers and disease severity or duration, but immunotherapy tends to decrease anti-GAD Ab titers.[3940]

Regarding treatment, most cases received symptomatic management, including benzodiazepines in 82% and baclofen in 48% of patients. Few cases reported requiring antiepileptics, intravenous sedation, or muscle relaxants. Mechanical ventilation was required in one patient. Immunotherapy was administered in majority of reported cases, including IVIg (48%), steroids (30%), rituximab (24%), mycophenolate mofetil (12%), azathioprine (6%), and plasmapheresis (6%). Surgical interventions were performed in cases with breast carcinoma and thymoma. Improvement was observed in 24% of patients with symptomatic treatment alone, while 72% required both symptomatic treatment and immunotherapy for improvement. Relapses were reported in 18% of patients. Treatment strategies for SPS include symptomatic management and disease-modifying immunotherapy.[31] Symptomatic management aims to alleviate stiffness, rigidity, and muscle spasms using drugs that enhance GABA effects, such as benzodiazepines and baclofen. Disease-modifying therapy targets the underlying immunologic mechanisms of SPS. IVIg is the most effective therapy, while the efficacy of plasma exchange is not fully established.[41] Corticosteroid effectiveness is uncertain in SPS. Rituximab has provided beneficial effect in non-randomized trials.[42] Other immunomodulating agents, including mycophenolate mofetil, azathioprine, cyclophosphamide, cyclosporine, tacrolimus, and sirolimus, have been reported with varying effectiveness.[43]

The reported efficacy of immunotherapy in SPS varies across studies ranging from 39% to 80%, despite this, a notable proportion of patients remain moderately disabled, with 30%-57% requiring assistance for mobility. Patients with GAD-associated cerebellar ataxia (CA) receiving immunotherapy promptly after diagnosis tend to exhibit better treatment responses. Approximately half of the patients still experience moderate to severe long-term complications. GAD-related epilepsy is often refractory to conventional antiepileptic drugs, immunotherapy remains the most promising treatment option for controlling seizures.[44] Lilleker et al. conducted a literature review on musicogenic epilepsy (ME) between 1884 and 2018 and found only two ME cases connected to anti-GAD antibodies; no patient was reported to have stiff-person syndrome. They concluded that the relation of anti-GAD antibodies to epilepsy remains uncertain and did not support the routine use of immunotherapy in patients with epilepsy and GAD antibodies.[45]

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form, the patient has given her consent for her images and other clinical information to be reported in the journal. The patient understands that her names and initials will not be published and due efforts will be made to conceal her identity, but anonymity cannot be guaranteed.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.
==== Refs
REFERENCES

1. Moersch FP Woltman HW Progressive fluctuating muscular rigidity and spasm (“stiff-man” syndrome); Report of a case and some observations in 13 other cases Proc Staff Meet Mayo Clin 1956 31 421 7 13350379
2. Asher R A woman with the stiff-man syndrome Br Med J 1958 1 265 6 13499919
3. Blum P Jankovic J Stiff-person syndrome: An autoimmune disease Mov Disord 1991 6 12 20 2005917
4. Dalakas MC Stiff person syndrome: Advances in pathogenesis and therapeutic interventions Curr Treat Options Neurol 2009 11 102 10 19210912
5. Solimena M Folli F Denis-Donini S Comi GC Pozza G De Camilli P Autoantibodies to glutamic acid decarboxylase in a patient with Stiff-man syndrome, epilepsy, and type I diabetes mellitus N Engl J Med 1988 318 1012 20 3281011
6. Grimaldi LM Martino G Braghi S Quattrini A Furlan R Bosi E Heterogeneity of autoantibodies in stiff-man syndrome Ann Neurol 1993 34 57 64 8517681
7. Markandeyulu V Joseph TP Solomon T Jacob J Kumar S Gnanamuthu C Stiff-man syndrome in childhood J R Soc Med 2001 94 296 7 11387424
8. Saravanan PK Paul J Sayeed ZA Stiff person syndrome and myasthenia gravis Neurol India 2002 50 98 100 11960163
9. Misra UK Maurya PK Kalita J Gupta RK Stiff limb syndrome: End of spectrum or a separate entity? Pain Med 2009 10 594 7 19302441
10. Agarwal PA Ichaporia NR Glutamic acid decarboxylase antibody-positive paraneoplastic stiff limb syndrome associated with carcinoma of the breast Neurol India 2010 58 449 51 20644278
11. Khade SS Deshmukh SS Dhonde PV Khadilkar SV Forty-year-old diabetic lady with tightness in lower limbs Ann Indian Acad Neurol 2012 15 15 8 22412266
12. Saigal R Goyal L Yadav R Agrawal A Mital P Patel B Stiff Person syndrome J Assoc Physicians India 2015 63 81 2
13. Chakravarthi S Goyal MK Lal V Pearls and Oysters: Tonic eye deviation in stiff-person syndrome Neurology 2015 84 e124 7 25917489
14. Renjen PN Chaudhari DM Clinical case reports Stiff Person syndrome with good treatment response to intrathecal baclofen J Clin Case Rep 2015 5 573
15. Maramattom BV Status spasticus and psoas muscle edema due to anti-GAD antibody associated stiff-man syndrome Indian J Crit Care Med 2015 19 493 5 26321813
16. Sharma CM Pandey RK Kumawat BL Khandelwal D Gandhi P A unique combination of autoimmune limbic encephalitis, type 1 diabetes, and Stiff person syndrome associated with GAD-65 antibody Ann Indian Acad Neurol 2016 19 146 9 27011652
17. Kumar MV Savida P Pediatric stiff-person syndrome with renal failure J Neurosci Rural Pract 2016 7 147 9 26933366
18. Nene Y Mehta T Pawar S Patil G Ichaporia NR A case of anti-glutamic acid decarboxylase-65 antibody positive stiff person syndrome presenting initially as acute peripheral vestibulopathy, leading to delayed diagnosis after multiple hospitalizations Cureus 2019 11 e6083 31853434
19. Shivaram S Nagappa M Seshagiri DV Mahadevan A Sinha S P-NE014. Electromyography in the diagnosis of stiff-person syndrome Clin Neurophysiol 2021 132 e92
20. Ray S Kamath V Rajesh KN Brachial monomelic amyotrophy as an initial manifestation of stiff person syndrome J Neurosci Rural Pract 2022 13 778 80 36743757
21. Kamaleshwaran KK Ramkumar E Senthilkumar E F-18 fluorodeoxyglucose positron emission tomography/computed tomography muscle uptake in antiglutamic acid decarboxylase antibody-positive Stiff-person syndrome Indian J Nucl Med 2023 38 162 4 37456188
22. Mandal A Thomas N Appaswamy PT Stiff-Person syndrome: A rare neurological disorder Indian J Case Reports 2023 9 134 7
23. McKeon A Robinson MT McEvoy KM Matsumoto JY Lennon VA Ahlskog JE Stiff-Man syndrome and variants: Clinical course, treatments, and outcomes Arch Neurol 2012 69 230 8 22332190
24. Rakocevic G Floeter MK Autoimmune stiff person syndrome and related myelopathies: Understanding of electrophysiological and immunological processes Muscle Nerve 2012 45 623 34 22499087
25. Dalakas MC Fujii M Li M McElroy B The clinical spectrum of anti-GAD antibody-positive patients with stiff-person syndrome Neurology 2000 55 1531 5 11094109
26. Clardy SL Lennon VA Dalmau J Pittock SJ Jones HR Jr Renaud DL Childhood onset of stiff-man syndrome JAMA Neurol 2013 70 1531 6 24100349
27. Sarva H Deik A Ullah A Severt WL Clinical spectrum of stiff person syndrome: A review of recent reports Tremor Other Hyperkinet Mov (N Y) 2016 6 340 26989571
28. Rakocevic G Alexopoulos H Dalakas MC Quantitative clinical and autoimmune assessments in stiff person syndrome: Evidence for a progressive disorder BMC Neurol 2019 19 1 30606131
29. Rakocevic G Raju R Semino-Mora C Dalakas MC Stiff person syndrome with cerebellar disease and high-titer anti-GAD antibodies Neurology 2006 67 1068 70 17000981
30. Pittock SJ Yoshikawa H Ahlskog JE Tisch SH Benarroch EE Kryzer TJ Glutamic acid decarboxylase autoimmunity with brainstem, extrapyramidal, and spinal cord dysfunction Mayo Clin Proc 2006 81 1207 14 16970217
31. Baizabal-Carvallo JF Jankovic J Stiff-person syndrome: Insights into a complex autoimmune disorder J Neurol Neurosurg Psychiatry 2015 86 840 8 25511790
32. Thomas S Critchley P Lawden M Farooq S Thomas A Proudlock FA Stiff person syndrome with eye movement abnormality, myasthenia gravis, and thymoma J Neurol Neurosurg Psychiatry 2005 76 141 2 15608018
33. Tanaka H Matsumura A Okumura M Kitaguchi M Yamamoto S Iuchi K Stiff man syndrome with thymoma Ann Thorac Surg 2005 80 739 41 16039251
34. Rosin L DeCamilli P Butler M Solimena M Schmitt H-P Morgenthaler N Stiff-man syndrome in a woman with breast cancer: An uncommon central nervous system paraneoplastic syndrome Neurology 1998 50 94 8 9443464
35. Balint B Bhatia KP Stiff person syndrome and other immune-mediated movement disorders-new insights Curr Opin Neurol 2016 29 496 506 27262149
36. Meinck HM Faber L Morgenthaler N Seissler J Maile S Butler M Antibodies against glutamic acid decarboxylase: Prevalence in neurological diseases J Neurol Neurosurg Psychiatry 2001 71 100 3 11413272
37. Saiz A Blanco Y Sabater L González F Bataller L Casamitjana R Spectrum of neurological syndromes associated with glutamic acid decarboxylase antibodies: Diagnostic clues for this association Brain 2008 131 2553 63 18687732
38. Manto M Honnorat J Hampe CS Guerra-Narbona R López-Ramos JC Delgado-García JM Disease-specific monoclonal antibodies targeting glutamate decarboxylase impair GABAergic neurotransmission and affect motor learning and behavioral functions Front Behav Neurosci 2015 9 78 25870548
39. Rakocevic G Raju R Dalakas MC Anti-glutamic acid decarboxylase antibodies in the serum and cerebrospinal fluid of patients with stiff-person syndrome: Correlation with clinical severity Arch Neurol 2004 61 902 4 15210528
40. Dalakas MC The role of IVIg in the treatment of patients with stiff person syndrome and other neurological diseases associated with anti-GAD antibodies J Neurol 2005 252 Suppl 1 I19 25 15959668
41. Ortiz JF Ghani MR Morillo Cox Á Tambo W Bashir F Wirth M Stiff-person syndrome: A treatment update and new directions Cureus 2020 12 e11995 33437550
42. Baker MR Das M Isaacs J Fawcett PR Bates D Treatment of stiff person syndrome with rituximab J Neurol Neurosurg Psychiatry 2005 76 999 1001 15965211
43. Hadavi S Noyce AJ Leslie RD Giovannoni G Stiff person syndrome Pract Neurol 2011 11 272 82 21921002
44. Dade M Berzero G Izquierdo C Giry M Benazra M Delattre JY Neurological Syndromes Associated with Anti-GAD Antibodies Int J Mol Sci 2020 21 3701 32456344
45. Lilleker JB Biswas V Mohanraj R Glutamic acid decarboxylase (GAD) antibodies in epilepsy: Diagnostic yield and therapeutic implications Seizure 2014 23 598 602 24836709
