Atypical parkinsonism and intrathecal anti-glutamic acid decarboxylase antibodies – an unusual association: a case report

Stefanoni, Giovanni; Formenti, Anna Maria; Tremolizzo, Lucio; Stabile, Andrea; Appollonio, Ildebrando; Ferrarese, Carlo

doi:10.1186/s13256-020-02412-x

Cited by 3 publications

(2 citation statements)

References 6 publications

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“…We also found patients presenting with parkinsonism and diplopia in combination with typical neurological syndromes. Parkinsonism has been previously described with CSF-positive anti-GAD antibodies [17]. Eye movement abnormalities have been previously described in association with anti-GAD65 antibodies [18,19], resulting in diplopia, as described in two patients from our series.…”

Section: Discussionsupporting

confidence: 64%

Characterization of Anti-GAD65-Associated Neurological Syndromes: Clinical Features and Antibody Titers

Moura,

Sambayeta,

Sousa

et al. 2024

NeuroSci

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Introduction: Anti-GAD65 antibodies are associated with several neurological phenotypes. Antibody titers are increasingly recognized as useful in diagnosis and prognosis. Objective: To describe a Portuguese cohort of patients with anti-GAD65-associated neurological syndromes. Methods: Retrospective analysis of all patients with positive anti-GAD65 antibodies and associated neurological syndromes followed in a tertiary referral center. Results: Nineteen anti-GAD65 antibody-positive neurological patients were identified, 62.3% female, with a mean age of onset of 56.0 (SD = 13.3) years. Comorbid autoimmune disorders were present in seven patients. Six patients had limbic encephalitis (31.6%), four had epilepsy (21.1%), four had cerebellar ataxia (21.1%), and three had stiff-person syndrome (15.8%). Two patients presented with isolated cognitive dysfunction (executive and mnesic) in the absence of other neurological symptoms. The mean follow-up time was 24.0 (14.0–42.0) months, at the end of which the mean modified Rankin Scale (mRS) value was 2.0 (1.0–4.0). Screening for malignancies was negative in all patients. Serum quantitative analysis was carried out in 18 patients, 10 of whom showed titers above previously defined cut-off points (>10,000 IU/L for ELISA and >20 mmol/L for RIA). Quantitative CSF analysis was performed in nine patients, with four showing above-threshold titers. There was no association between anti-GAD65 levels and clinical phenotype or the final mRS values. High-dose intravenous methylprednisolone and oral prednisolone were the most common acute and chronic treatment regimens, respectively. Conclusion: Anti-GAD65 antibodies are associated with varied neurological syndromes, and antibody titers alone should not be used to exclude a disease.

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Section: Discussionsupporting

confidence: 64%

Characterization of Anti-GAD65-Associated Neurological Syndromes: Clinical Features and Antibody Titers

Moura,

Sambayeta,

Sousa

et al. 2024

NeuroSci

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“…Parkinsonism, namely, a combination of asymmetrically slowed movement, rigidity, and tremor, is an uncommon manifestation of an autoimmune condition but has been associated with anti-GAD65 antibodies. However, MSA-and PSPlook-alike disorders have been reported with GAD65, GAD67, glycine receptor, among other autoantibodies (20)(21)(22).…”

Section: Dr Butala (Movement Disorders and Ataxia Neurology)mentioning

confidence: 99%

Centripetal Nystagmus, Slow Saccades, Cerebellar Ataxia, and Parkinsonism in a Patient With Anti-GAD65-Associated Stiff Person Syndrome Spectrum Disorder

Hac¹,

Murphy²,

Butala³

et al. 2023

Journal of Neuro-Ophthalmology

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:A 68-year-old woman with positional dizziness and progressive imbalance presented for vestibular evaluation. Examination was notable for spontaneous downbeat nystagmus (DBN), horizontal and vertical gaze-evoked nystagmus (GEN) with centripetal and rebound nystagmus, and positional apogeotropic nystagmus. There was also mild–moderate slowing of saccades horizontally and vertically and poor fast phases with an optokinetic stimulus. Further consultation by a movement disorder specialist uncovered asymmetric decrementing bradykinesia and rigidity, masked facies, and a wide-based stance without camptocormia. Screening serum laboratory results for metabolic, rheumatologic, infectious, heavy metal, endocrine, or vitamin abnormalities was normal. Surveillance imaging for neoplasms was unremarkable, and cerebrospinal fluid (CSF) analysis was negative for 14-3-3 and real-time quaking-induced conversion (RT-QuIC). However, her anti-glutamic acid decarboxylase-65 (GAD65) immunoglobulin G (IgG) level was markedly elevated in serum to 426,202 IU/mL (reference range 0–5 IU/mL) and in CSF to 18.1 nmol/L (reference range <0.03 nmol/L). No other autoantibodies were identified on the expanded paraneoplastic panel. The patient was referred to neuroimmunology, where torso rigidity, spasticity, and significant paravertebral muscle spasms were noted. Overall, the clinical presentation, examination findings, and extensive workup were consistent with a diagnosis of anti-GAD65-associated stiff person syndrome-plus (musculoskeletal plus cerebellar and/or brainstem involvement). She was subsequently treated with intravenous immunoglobulin (IVIg) and has been stable since commencing this therapy. In patients with centripetal nystagmus, especially in association with other cerebellar findings, an autoimmune cerebellar workup should be considered.

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Neurological Manifestations of Glutamic Acid Decarboxylase Autoimmunity in Indian Patients

Thevarkalam,

Kannoth,

Nambiar

et al. 2023

Annals of Indian Academy of Neurology

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Objective: To study the neurological manifestations of glutamic acid decarboxylase (GAD 65) autoimmunity in Indian patients. Methods: Retrospective study conducted in a tertiary care referral hospital in South India. Patients who tested positive for GAD 65 antibodies from February 2013 to July 2019 were included. Results: We identified 922 patients who underwent GAD 65 testing, of which 81 tested positive (8.78%) [mean age 55.42 years (SD 17.39, range 9–86 years, median age 57 years)]. Males (n = 47) outnumbered the females (n = 34). All the GAD values measured were <5000 IU/ml. There were 34 cases (42%) of atypical parkinsonism (16/34, 47% fulfilled the diagnostic criteria for autoimmune atypical parkinsonism) in our series forming the most common group with GAD 65 positivity, followed by autoimmune encephalitis (8 cases, 9.88%). Men were more affected with atypical parkinsonism (22/34; 64.70%), stiff person syndrome (2/3; 66.66%), and neuropathy (4/7; 57.1%) while women were more with autoimmune encephalitis (6/8; 75%). Eighteen (22.6%) had underlying autoimmunity (three had type 1 diabetes mellitus). Six (7.4%) had underlying neoplasm. Thirty-three out of 43 patients responded to immunotherapy (76.74%). Five had spontaneous improvement. Conclusion: Glutamic acid decarboxylase65 antibody values were much lower in our study population. Male-dominant autoimmunity was seen unlike that in Western literature. The most striking was the high preponderance of atypical parkinsonism in GAD 65-positive patients. We also found that GAD 65 positivity is a useful marker for a positive response to immunotherapy in suspected autoimmune neurological syndromes irrespective of their titers.

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Atypical parkinsonism and intrathecal anti-glutamic acid decarboxylase antibodies – an unusual association: a case report

Cited by 3 publications

References 6 publications

Characterization of Anti-GAD65-Associated Neurological Syndromes: Clinical Features and Antibody Titers

Characterization of Anti-GAD65-Associated Neurological Syndromes: Clinical Features and Antibody Titers

Centripetal Nystagmus, Slow Saccades, Cerebellar Ataxia, and Parkinsonism in a Patient With Anti-GAD65-Associated Stiff Person Syndrome Spectrum Disorder

Neurological Manifestations of Glutamic Acid Decarboxylase Autoimmunity in Indian Patients

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