Levodopa-responsive progressive encephalomyelitis with rigidity and myoclonus associated with glycine receptor antibodies

•New dopa-responsive phenotype expands the spectrum of GlyR antibody-associated PERM syndrome.•Appendicular rigidity with axial hypotonia and oculomotor abnormalities suggested hypodopaminergic tone.•Downstream effects antibody may interfere dopamine network. Progressive encephalomyelitis myoclonus (PERM) syndrome is a rare autoimmune encephalitis, often associated glutamic acid decarboxylase (GAD), dipeptidyl-peptidase–like protein 6 (DPPX), or glycine receptors (GlyR) antibodies [[1]Carvajal-González A. Leite M.I. Waters P. Woodhall M. Coutinho E. Balint B. Lang Pettingill Carr Sheerin U.M. Press R. Lunn M.P. Lim Maddison Meinck H.M. Vandenberghe W. Vincent Glycine receptor in related syndromes: characteristics, clinical features outcomes.Brain. 2014; 137: 2178-2192Crossref PubMed Scopus (271) Google Scholar]. The most relevant are rigidity, myoclonus, dysautonomia, brainstem dysfunction Symptoms during acute phase can be severe, response to immunotherapy variable We report case poor which levodopa resulted marked improvement, facilitating his subsequent rehabilitation. This 41-year-old man prior history hepatitis C acutely developed dizziness, headache, vomiting. A diagnosis peripheral vestibular was made an emergency evaluation. Recrudescence vertigo, new left facial nerve palsy, progressive respiratory distress evolved on next day, requiring admission intensive care unit (ICU) for endotracheal intubation. Over few days, he manifested fixed limbs episodes generalized bilateral ptosis (prevalent right eye), persistent gaze deviation, dysphagia, drowsiness, nystagmus, dysautonomic (neurogenic bladder hypertension). Routine laboratory investigations, including search onconeural commercial test (Euroimmun, Lubeck, Germany), electroencephalography, brain MRI were unremarkable. Lumbar puncture showed intrathecal IgG synthesis (IgG-index = 0.8; unique-to-CSF oligoclonal bands). Treatment high-dose steroids followed by intravenous immunoglobulin only function sufficient interrupt mechanical ventilation but without motor improvement. He discharged from ICU after 3 months transferred rehabilitation center. However, physical therapy hampered due persistence severe compounded intermittent (Video 1, online) weakness neck flexor muscles. following Supplementary data this article.https://www.prd-journal.com/cms/asset/e0a87163-a734-413b-9cee-cfd63c217ad5/mmc2.mp4Loading ...(mp4, 4.71 MB) Download video https://www.prd-journal.com/cms/asset/e0a87163-a734-413b-9cee-cfd63c217ad5/mmc2.mp4Loading combination hypotonia, common childhood disorders selected disruptions metabolism pathways. Therefore, 4 unsuccessful unresponsiveness GABAergic drugs (baclofen, clonazepam), treated low doses levodopa/benserazide up 300/75 mg/daily, improvement within week 2, online). It at stage that identified serum CSF using in-house live cell-based assay taper led reemergence promptly corrected when restarted. After 10 while levodopa, patient achieved symptom resolution except presence mild neurogenic 3, has remained clinically stable 24 follow-up, despite serum. DATscan obtained normal (unable obtain previously given critical condition inability tolerate such procedure). absence C-associated cancers conditions confirmed stage. prompted review literature, showing variety disorders, parkinsonism other extrapyramidal [[2]Piquet A.L. Khan Warner J. Wicklund Bennett J.L. Leehey M.A. Seeberger L. Schreiner T.L. Paz Soldan M.M. Clardy S.L. Novel syndrome: series 17 cases.Neurol Neuroimmunol Neuroinflamm. 2019; 6: e592Crossref (20) Scholar] (Table 1; material 1).Table 1Antiglycine features: literature review.Clinical featuresFrequencySymptomsTotal: 152Spasm/stiffness/rigidity/myoclonus (neck, trunk limb muscles)96 (63%)Bulbar disturbance (dysphagia, dysarthria)44 (29%)Oculomotor (gaze eyelid ptosis, diplopia, nystagmus)39 (26%)Startle reaction38 (25%)Epilepsy (generalzid, mesial temporal lobe epilepsy, focal)27 (18%)Autonomic disturbance26 (17%)Cognitive impairment23 (15%)Psychiatric symptoms23 (15%)Sensory symptoms21 (14%)Respiratory failure9 (6%)Parkinsonism3 (2%)Other movement (ataxia, chorea, hemiballism)24 (16%)Age onsetTotal: 151Range1–79GenderTotal: 151Male78 (52%)Female73 (48%)Disease-modifying treatmentTotal: 96Steroids65 (68%)Intravenous immunoglobulin61 (63%)Immunosuppressants30 (32%)Plasma exchange28 (30%)Monotherapy31 (32%)Polytherapy65 (68%)Response 125Partial/good108 (86%)Poor/no response11 (9%)Death6 (5%)Associate ongoing conditionsTotal: 49Thyroiditis16 (33%)Diabetes7 (14%)Vitiligo6 (12%)Gastrointestinal (ulcerative colitis, celiac disease)3 (6%)Psoriasis2 (4%)Connective tissue disease2 (4%)Systemic sarcoidosis2 (4%)Vasculitis1 (2%)Sjogren's syndrome1 (2%)Addison disease1 (2%)Pernicious anemia1 (2%)Systemic (not specified)7 (15%)Associate tumorsTotal: 11Breast2 (18%)Thymoma5 (46%)Lymphoma2 (18%)Ovarian adenocarcinoma1 (9%)Small cell lung cancer1 (9%) Open table tab articlehttps://www.prd-journal.com/cms/asset/36b3d154-c7fa-4ed1-af48-dabc0cee4c2d/mmc3.mp4Loading 2.08 https://www.prd-journal.com/cms/asset/8b043bf2-87ad-4646-8c61-753f92eac1c9/mmc4.mp4Loading 1.97 https://www.prd-journal.com/cms/asset/36b3d154-c7fa-4ed1-af48-dabc0cee4c2d/mmc3.mp4Loading disorder life-threatening if not 1). In our patients, recovery delayed insufficient benefit immunomodulatory treatments, facilitated high levodopa. well-known childhood-onset tyrosine hydroxylase [[3]Zafeiriou D.I. Willemsen Verbeek Vargiami Ververi Wevers Tyrosine deficiency course.Mol. Genet. Metabol. 2009; 97: 18-20Crossref (30) sepiapterin reductase deficiencies [[4]Abeling N.G. Duran Bakker H.D. Stroomer Thöny Blau N. Booij Poll-The B.T. Sepiapterin autosomal recessive DOPA-responsive dystonia.Mol. 2006; 89: 116-120Crossref (50) Such syndromic ascertainment further supported sustained gaze, feature could have well been characterized as oculogyric crisis [[5]Slow E.J. A.E. Oculogyric crises: phenomenology, etiology, pathogenesis, treatment. Mov Disord., 2017: 193-202Google To best knowledge, first responsive abnormalities, suggesting interaction between control networks. GlyRs striatum, globus pallidus, substantia nigra (both pars compacta reticulata), increase release application [[6]Waldvogel H.J. Baer K. Allen K.L. Rees Faull R.L. human brain: immunohistochemical study.J. Comp. Neurol. 2007; 502: 1012-1029Crossref (35) As result, supply both direct indirect pathways reduced antibodies, disruption glycinergic neurotransmission mediated [[7]Crisp S.J. Dixon C.L. Jacobson Chabrol Irani S.R. Leschziner G. Slaght Kullmann D.M. autoantibodies disrupt inhibitory neurotransmission.Brain. 142: 3398-3410Crossref exacerbation hours discontinuation rapid upon reexposure supports efficacy treatment patient. Although it performed disease, patient's negative favors notion dopa-responsiveness functional caused rather than underlying dopaminergic neuronal loss. conclusion, phenotypic PERM, abnormalities. exquisite markedly efforts required maximizing recovery. Informed written consent: Patient gave informed consent publication report. Video: subject included signed face anonymization. thank Professor Angela (Oxford University) providing plasmid used establish live-CBA. supplementary article: .docx (.02 Help docx files Multimedia component 1 Andrea Sturchio, Lucia Princiotta Cariddi, Daniela Biacchi, Marco Mauri no disclosures. Matteo Gastaldi received honoraria Roche. Alberto J Espay grant support NIH Michael Fox Foundation ; personal compensation consultant/scientific advisory board member Abbvie, Neuroderm, Neurocrine, Amneal, Adamas, Acadia, Acorda, InTrance, Sunovion, Lundbeck, USWorldMeds; publishing royalties Lippincott Williams & Wilkins, Cambridge University Press, Springer; USWorldMeds, American Academy Neurology, Movement Disorders Society. Diego Franciotta fundings Italian Ministry Health ‘Ricerca Corrente’ 2017–2019 (Grant code: RC1812C ). Maurizio Versino donation academic funds Chiesi Farmaceutici SpA .