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- Movement Disorders (other Than Parkinsons)
- Medical Management
- Drugs: Cns (not Psychiatric)
A 72-year-old Afro-Caribbean woman presented with diplopia, vertigo, intermittent vomiting, progressively worsening ataxia (video 1) and nystagmus (video 2, segment 1) over a period of 4 months. There was a 2-year history of type 2 diabetes mellitus and hypothyroidism being treated with oral metformin 500 mg, gliclazide 80 mg two times per day and L-thyroxine 0.1 mg daily. She denied exposure to chemicals or recreational drugs. Social, family and sexual history were insignificant.
Her body mass index was 24 kg/m2. The Mini Mental State Examination (MMSE) score was 30/30. Cerebellar gait ataxia with an ample sustentation base was present. This worsened over 4 weeks, leading to a score of 26/40 on the scale for the assessment and rating of ataxia (SARA). Dysmetria and dysdiadochokinesis were also prominent in all limbs. Bilateral gaze-evoked nystagmus was noted in the primary position, in horizontal, upbeat and down beat directions but this was not torsional (video 2, segment 1). Dysarthria, intention tremor, spinal cord long tract signs and rigidity were absent. The rest of the physical examination was normal.
Extensive medical investigations ruled out underlying endocrine, autoimmune, vasculitic, infectious and neoplastic illnesses. Glycosylated haemoglobin (Hb1Ac) level of 5.5% was normal. Haematologic and metabolic status, hepatic and renal function tests, collagen vascular tests, tumour markers, retroviral and syphilitic serological tests and cerebellar antibody panel for neoplasm were normal. High levels of glutamic acid decarboxylase antibodies (GAD-Abs) at 502.4 U/mL (reference range positive above 10 U/mL) with mildly elevated anti-thyroid antibodies (TPO AB) at 37.18 IU/mL (reference range, 0–35 IU/mL) were noted. MRI of the brain with angiography and venography, MRI of the spinal cord, computerised tomographic scans of the chest, abdomen and pelvis, mammography, oesophgogastroduodenoscopy and colonoscopy were normal. Positron emission tomography scan and islet cell antibody testing were unavailable. Other immune-mediated cerebellar ataxias including gluten ataxia, paraneoplastic cerebellar degeneration, Hashimoto’s encephalopathy and other differentials were also considered (table 1).
GAD-Abs associated cerebellar ataxia with nystagmus was diagnosed based on the neuroclinical manifestations, elevated serum GAD-Abs, MRI findings, exclusion of other diseases with further support from the patient’s clinical and biochemical response to immunomodulation. Treatment with steroids and azathioprine over 4 months demonstrated an improvement of nystagmus (video 2, segment 2), partial resolution of diplopia, vertigo, dysmetria, dysdiadochokinesis and ataxia with an increase in the SARA score to 35/40. GAD-Abs level decreased to 318.4 U/mL after 6 months treatment. Subsequently, human immune globulin and/or plasmapheresis treatment was declined.
GAD-Abs spectrum disorder includes limbic encephalitis, opsoclonus-myoclonus-ataxia syndrome, palatal myoclonus, epilepsy, stiff person syndrome, encephalomyelitis with rigidity, Guillain-Barré and myasthenia like syndromes, cerebellar ataxia with or without nystagmus and is considered part of the group of polyglandular autoimmune illnesses, that includes diabetes mellitus, myasthenia gravis, thyroiditis and pernicious anaemia. The cerebrospinal fluid analysis may be normal or may show oligoclonal bands, mild pleocytosis and intrathecal synthesis of GAD-Abs, in some cases. Cerebellar ataxia associated with GAD-Abs is rare, particularly when accompanied by nystagmus.1–3
This report represents the first documented case of this clinical entity from the West Indies.
Glutamic acid decarboxylase antibodies (GAD-Abs)-associated cerebellar ataxia is a part of an expanding spectrum of neurological disorders associated with the GAD enzyme needed to convert the excitatory amino acid glutamate into the inhibitory neurotransmitter gamma-aminobutyric acid.
Cerebellar ataxia associated with GAD-Abs can be diagnosed based on the neuroclinical manifestations and elevated GAD-Abs, with further support from the patient’s response to immunomodulation.
Cerebellar ataxia with or without nystagmus associated with GAD-Abs is a potentially treatable syndrome using immunomodulation.
GAD-Abs should be sought not only in patients with polymorphic, persistent or refractory neurological syndromes but also with associated cancer and polyglandular autoimmune illnesses.
Contributors KR: conceived the manuscript. AJR: wrote the first draft and prepared the videos. KR, AJR, KA and NR: worked on subsequent revisions. All authors assume responsibility for the final manuscript.
Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.
Competing interests None declared.
Provenance and peer review Not commissioned; externally peer reviewed.
Patient consent for publication Obtained.