Figure 1
PRISMA flow diagram of the study.
*Consider, if feasible to do so, reporting the number of records identified from each database or register searched (rather than the total number across all databases/registers).
**If automation tools were used, indicate how many records were excluded by a human and how many were excluded by automation tools.
Source: Page MJ, et al. BMJ 2021; 372: n71. doi: 10.1136/bmj.n71.
This work is licensed under CC BY 4.0. To view a copy of this license, visit https://creativecommons.org/licenses/by/4.0/.
Table 1
Brief description of different phenotypes of dystonia in different autoimmune disorders.
| ANTIBODY | PREVALENCE OF DYSTONIA | AGE OF INVOLVEMENT | PATTERN OF DYSTONIA | OTHER ASSOCIATED NEUROLOGICAL SYMPTOM OR MOVEMENT DISORDER | INVESTIGATION | TREATMENT OUTCOME |
|---|---|---|---|---|---|---|
| NMDA Receptor Encephalitis | 20% | 6–18 years | Phenotype 1- Classical- In Children polysymptomatic MD, orofacial lingual dyskinesia, stereotypes. Phenotype 2-Monosymptomatic MD Limb or OMD, hemidystonia in adults | Chorea, Steriotypies, Psychiatric and behavioral features, dysautonomia. Oculogyric crisis in children | MRI- Normal or non-specific changes. T2/FLAIR hyperintensity in mesial temporal lobe, cerebral and cerebellar cortex PET- Both hypo and hypermetabolism of the affected region depending on time and severity of presentation. EEG- Generalized Slowing | IVMPS IVIg PLEX Rituximab Good response to IT |
| LGI 1 associated encephalitis | 40% | 40–70 years | FBDS | Cognitive decline, Insomnia, hyponatremia | MRI – Bitemporal hyperintensity, T2 signal changes in basal ganglia. EEG- normal | IVMPS IVIg Good response to first line IT |
| Anti Ri associated Encephalitis | 17- 33% | 40–80 years | Craniocervical Dystonia (Jaw closing dystonia, torticollis) Exclusively occurring in the context of breast cancer | Cerebellar ataxia, OMAS | MRI- Normal or T2/FLAIR signal changes in brainstem, upper cervical cord, basal ganglia, mesial temporal lobes. | Good response to symptomatic therapy than IT or tumor removal. |
| Anti IgLon5 associated Encephalitis: | 26% | 40–90 years | Phenotype 1 – painful craniocervical dystonia Associated with dystonic tremor and myoclonus of same region. Phenotype 2 – Subtle Limb dystonia, upper limb, and finger, never presenting complaint | Chorea, PSP like phenotype, SPS like, facial dyskinesia, cerebellar ataxia | MRI – normal or cerebral atrophy | Craniocervical Dystonia less responsive to IT, required tetrabenazine, Botox Limb dystonia more responsive to IT |
| Anti-GAD65 antibody-associated Encephalitis: | 0.03% | 5–83 years | Phenotype 1- insidious onset lower limb predominant limb dystonia occurring more in 5th decade (47) and older. Phenotype-2 subacute onset craniocervical dystonia seen in middle aged patients | SPS, Epilepsy, LE, ataxia, cognitive decline, myelopathy Associated with systemic autoimmune disease T1DM, Thyroid disease | MRI – Normal or disproportionate cerebral atrophy EMG –to differentiate from SPS. | Good outcome with IVIg in young Older patient respond to symptomatic therapy more. |
| Anti GABA receptor Encephalitis: | 35% | 10 month-63 years | Closely follows NMDA encephalitis. | Refractory seizure, cognitive decline | MRI – Multifocal cortical and subcortical FLAIR hyperintensities | Good response to IT, poor response to symptomatic local therapy |
| Anti D2R Encephalitis | Usually hemidystonia with a dystonic tremor Some have oro- mandibular Dystonia. Progress to status Dystonicus | Tics, parkinsonism, psychiatric or sleep disturbance, seizure. | MRI – Bilateral Basal Ganglia FLAIR hyperintensity, striatal necrosis in later stage FDG PET – hypermetabolism of the affected region | Good response to IT (90% had complete or partial resolution), TS and Isolated psychosis group – symptomatic therapy | ||
| Anti PDE 10 A Encephalitis | Limited Case reports | 70 years (range 66–76); | Combined dystonia with other hyperkinetic movement disorders | Encephalopathy Often associated with cancer or follows treatment with immune checkpoint inhibitors (ICI). | MRI- Bilateral T2/FLAIR basal ganglia hyperintensities, leptomeningeal enhancements | Poor response to immunotherapy, cessation of ICI or treatment of cancer. |
| Anti Ma2 Encephalitis | Limited Case reports | 26–70 years | Jaw opening dystonia and left upper limb dystonia (as a part of MSA phenotype) | Limbic, diencephalic, brainstem encephalopathy, narcolepsy-cataplexy, eye movement abnormalities (60% had vertical gaze paresis evolved to total external ophthalmoplegia). Usually associated with testicular tumors. | MRI- T2/FLAIR signal changes in the bilateral or unilateral medial temporal lobe, hypothalamus, thalamus, mid-brain, pons, superior and middle cerebellar peduncle. PET – Hypermetabolism in the abnormal area. Low CSF hypocretin level | Poor response to combined immunotherapy and cancer treatment. One-third had a partial response to treatment with the majority of them relapsed later. |
| Anti CRMP5 | Limited Case Reports | 60–70 years | Limb dystonia associated with other hyperkinetic movements (chorea, ataxia) | Limbic Encephalitis, chorea, ataxia, peripheral neuropathy, myelopathy optic neuritis or retinitis. | MRI – Can be normal or multiple T2/FLAIR high signal foci, mainly involving the basal ganglia, medial temporal lobe, white matter, cerebellum, insula, optic nerve, thalamus, and frontal lobe. PET- Hypometabolism in bilateral caudate, frontoparietal lobes. | Poor response to immunotherapy. However early and aggressive anti-tumor plus immunotherapy is required. |
| MOG Antibody Disease | Limited Case Reports | 2–28 years | Combined dystonia including orofacial and limb dystonia associated with encephalopathy, and seizure. | Fever, encephalopathy, seizure, paresis, headache. | MRI- Multifocal T2/FLAIR white matter, cortical, spinal cord hyperintensity | Good response to steroids and other second-line immunotherapy and local symptomatic therapy as required. |
| Anti mGluR5 | Limited Case Reports | Second to third decade | Combined generalized and orofacial dystonia with encephalopathy | Limbic Encephalitis, hallucination, cognitive decline, refractory seizure. | MRI – T2/FLAIR hyperintensities in the limbic region or extra limbic regions, meningeal enhancements. | Good response to combined immunotherapy and anti-tumor therapy. |
| Sjogren Syndrome | 2.2% | 36–57 years | Phenotypes: 1. Late-onset (median 57.5 years) slowly progressive Craniocervical dystonia OR 2. Unilateral painful paroxysmal dystonic attacks of one or both limbs (duration: <2 min, frequency: several times/day) | Cognitive decline, Neuropathy, Aseptic meningitis, cranial neuropathy. | Phenotype 1: MRI: normal, or multiple subcortical T2- hyperintensities Phenotype 2: MRI: ischemic or inflammatory brain/spinal lesions | Phenotype 1: Positive outcome following immunotherapy Phenotype 2: Good outcome with immunotherapy and symptomatic treatments (CBZ/Phenytoin) |
| Systemic Lupus Erythematosus (SLE) | 8–65 years | Two phenotypes 1.MR Positive- Middle aged male with complex hyperkinetic movement disorder 2. MR negative – Female, extremes of ages, isolated focal or hemidystonia | MR positive cases- chorea, parkinsonism, myoclonus, athetoid movements. | MRI -contralateral or bilateral Basal ganglia FLAIR changes Antibody panel- ANA (speckled pattern), high positivity of Anti dsDNA, normal C3, C4 | MR positive- very good response to IT. MR Negative – Variable response to IT | |
| Antiphospholipid Antibody Syndrome | 7–76 years | Isolated focal Dystonia or Hemidystonia | Chorea, parkinsonism | MRI – Basal ganglia infarction T2/FLAIR hyperintense lesion Antibody panel – aCL IgG was positive in all patients. B2GP and LA were positive in complex MD cases | Mixed response to IT with anticoagulation | |
| Neuro Behcet’s Disease | 6% | 20–30 years | Paroxysmal painful focal dystonia or hemidystonia | Ataxia, Brainstem signs | MRI – T2/FLAIR high signal in basal ganglia, brain stem, cerebral cortex | Good response to IT and D2 Blocker |
Figure 2
Clinical pattern of dystonia associated with autoimmune disorder.
Figure 3
Clinical approach to dystonia in autoimmune disorders.
Table 2
Search Strategy in Pubmed.
| AND | OR | ||||
|---|---|---|---|---|---|
| DATABASE | SEARCH TERM 1 | SEARCH TERM 2 | SEARCH TERM 3 | ||
| Pubmed | NMDA Encephalitis | Dystonia/Dyskinesia | Movement Disorder | ||
| LGI1 Associated Encephalitis | Dystonia/Dystonic seizure | Movement Disorder | |||
| Anti Ri associated encephalitis | Dystonia | Movement Disorder | |||
| Anti IgLon5 associated encephalitis: | Dystonia | Movement Disorder | |||
| Anti GAD65 antibody associated Encephalitis: | Dystonia | Movement Disorder | |||
| Anti GABA receptor Encephalitis: | Dystonia/Dyskinesia | Movement Disorder | |||
| Anti D2R Encephalitis | Dystonia | Movement Disorder | |||
| Anti PDE 10 A Encephalitis | Dystonia | Movement Disorder | |||
| Anti Ma2 Encephalitis | Dystonia | Movement Disorder | |||
| Anti CRMP5 | Dystonia | Movement Disorder | |||
| MOG Antibody Disease | Dystonia | Movement Disorder | |||
| Anti mGluR5 | Dystonia | Movement Disorder | |||
| Sjogren Syndrome | Dystonia | Movement Disorder | |||
| Systemic Lupus Erythematosus (SLE) | Dystonia | Movement Disorder | |||
| Neurobehcet’s Disease | Dystonia | Movement Disorder |