<scp>PINK</scp>‐1 Parkinson's Disease Presenting with Dystonic Head Tremor

Dystonia and parkinsonism are two conditions with many pathophysiological overlaps.1 The occurrence of cervical dystonia(CD) before the onset of PD is not common but has been described.2, 3 Here we report a peculiar case of PINK-1 associated YOPD presenting as dystonic head tremor, even before the appearance of parkinsonian symptoms. Notably, treatment with Levodopa significantly improved both parkinsonism and head tremor. A 34-year-old man presented with complaints of head tremor of 1-year duration and slowness and stiffness of the left upper limb of 6 months duration. There was no history suggestive of parkinsonism, head tremor, or dystonia in the family. Clinical examination revealed “no-no” type of dystonic head tremor, varying with neck movements and increasing with speech. He had right torticollis with left laterocollis without restricted neck movements [Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS)-12]. He also had bradykinesia and rigidity of his left upper and lower limbs with reduced arm swing on the left [Unified Parkinson's Disease Rating Scale (UPDRS-III)-12] (Video 1-segment A). The magnetic resonance image (MRI) of the brain, including susceptibility-weighted images was normal. Serum ceruloplasmin, ferritin, lactate and 24 h urine copper levels were normal. Clinical exome sequencing detected a nonsense homozygous pathogenic variant (c.1212C > A) in the exon 6 of the PINK1 gene (rs747239996). This variant resulted in a stop codon and premature truncation of the protein at codon 404 (p.Tyr404Ter). The anti-parkinsonian medications were initiated and optimized to Levodopa 300 mg/day and Pramipexole 0.75 mg/day. There was a significant improvement in bradykinesia, rigidity (UPDRSIII - 4) and dystonic head tremor (TWSTRS-6) (Video 1-segment B). Dystonia is a common occurrence in the context of parkinsonism, with examples including foot dystonia in YOPD, anterocollis in multisystem atrophy, hand dystonia in corticobasal degeneration and blepharospasm in progressive supranuclear palsy. Others in the spectrum include neurodegeneration with brain iron accumulation (NBIA), metabolic disorders like Wilson's disease, amino acidopathies, organic acidurias, mitochondrial cytopathies and storage disorders, genetic dystonias like ATP1A3 mutation and PRKRA mutations, infectious encephalitis like Japanese encephalitis, autoimmune diseases like CNS lupus, and anti-NMDAR encephalitis, drug induced dystonia-parkinsonism, and neurotransmitter deficiencies. In a large series, dystonia was the initial symptom of PD in 5 of 207 (2.4%) patients, and for disease onset below 40 years, the percentage was as high as 14%.4 In the three common forms of autosomal recessive parkinsonism caused by mutations in parkin(PARK2), PINK1(PARK6), or DJ-1(PARK7) gene, the phenotype is usually characterized by levodopa-responsive parkinsonism, and levodopa induced dyskinesias without atypical features.5 Mitochondrial dysfunction, characterized by impaired mitophagy, has been linked to the pathogenic variants in these genes. Even though there are reports of CD in PD, not responsive to levodopa,3 there are rare instances of complete resolution of CD after initiating L-Dopa for PD.6 The head tremor in PD persists at rest and disappears with action unlike dystonic head tremor seen in our patient.7 The case describes an unusual finding of dystonic head tremor as the presenting feature of PINK-1 variant, reiterating the pathophysiological overlaps between dystonia and parkinsonism, importance of detailed clinical evaluation to check for accompanying parkinsonism and a possible role for levodopa in treatment. (1) Research project: A. Conception, B. Organization, C. Execution; (2) Data Analysis: A. Design B. Execution C. Review and Critique; (3) Manuscript Preparation: A. Writing of the first draft B. Review and Critique. A.V.: 1A, 1B, 1C, 3A. P.K.S.: 1B, 3B. P.S.: 1A, 3B. D.K.P: 1B, 1C, 3B. S.K.: 1A, 1B, 1C, 3B. Authors are thankful for Ms. Geetha R's contribution in acquisition of the patient's video. Authors are also grateful to the patient who consented to the publication of his clinical details. Ethical Compliance Statement: Written informed consent was taken from the patient. The authors confirm that the approval of the institutional review board was not required for this work. We confirm that we have read the journal's position on issues involved in ethical publication and affirm that this work is consistent with those guidelines. Funding Sources and Conflicts of Interest: No specific funding was received for this work. The authors declare that there are no conflicts of interest relevant to this work. Financial Disclosures for the Previous 12 Months: The authors declare that there are no additional disclosures to report.

Récupéré en direct depuis OpenAlex et désinversé. Les résumés ne sont pas conservés dans cette base de données : les index inversés représentent 8,6 Go des 9,3 Go de texte de la base, et le serveur dispose de 13 Go libres.