When Stroke-Like Brain Lesions Mask a Treatable Genetic Ataxia

Every so often, a single clinical case does more than describe the misfortune of one patient; it exposes a diagnostic trap that could be waiting for physicians anywhere. A new letter in the Journal of Neurology, authored by Sarika Mutyala, Prateek, Ashmit Gupta and Chiranjeevi Kona from medical institutions across India, describes exactly such a scenario. The clinicians report a patient whose recurrent brain lesions, scattered across the posterior regions of the cerebrum and seemingly resembling strokes, ultimately turned out to be the outward face of a rare genetic disorder: COQ8A-related coenzyme Q10 deficiency. It is a condition that, unlike many causes of progressive neurological decline, may respond to a surprisingly simple therapy, and one that can look deceptively like an entirely different disease on brain imaging.

The core of the report lies in that disconnect between appearance and underlying cause. Stroke-like lesions, particularly when they recur and cluster in the posterior brain territories, typically send clinicians down a well-worn diagnostic path toward cerebrovascular disease, mitochondrial encephalopathy, or inflammatory conditions such as posterior reversible encephalopathy syndrome. The letter’s authors detail a clinical course in which the patient’s lesions heralded a condition few emergency departments or even stroke units would place high on their differential list. By the time the correct diagnosis was reached, the case had already accumulated the hallmarks of an ataxia syndrome, the slowly progressive loss of coordination that defines the cerebellar disorders.

COQ8A, once known by the name ADCK3, encodes a protein kinase that sits at the heart of the biochemical machinery producing coenzyme Q10, also called ubiquinone. This small, lipid-soluble molecule is not a genetic curiosity; it is an essential shuttle in the mitochondrial electron transport chain, ferrying electrons between the complexes that generate most of the cell’s energy in the form of ATP. Biallelic mutations in COQ8A disrupt this production line, and the result is primary coenzyme Q10 deficiency, one of a small family of inherited disorders in which the body’s own ubiquinone manufacturing falters. Because neurons, and particularly cerebellar Purkinje cells, are metabolically voracious, the clinical signature often emerges as cerebellar ataxia.

The condition first entered the medical literature in 2008, when Lagier-Tourenne and colleagues identified ADCK3 mutations in families with recessive ataxia associated with coenzyme Q10 deficiency, and Mollet and coworkers independently linked CABC1, the same gene under another name, to ubiquinone deficiency with cerebellar ataxia and seizures. In the years since, the phenotype has been progressively clarified. A multicenter study published in Annals of Neurology in 2020 by Traschütz and colleagues delineated the clinico-genetic, imaging and molecular features of COQ8A-ataxia in a cohort of 59 patients, establishing a core phenotype of slowly progressive gait ataxia with variable additional features, including epilepsy, cognitive involvement and, in some individuals, dystonia. That study remains a cornerstone for clinicians who suspect the disorder.

What makes the new Indian case noteworthy is the prominence of stroke-like episodes in the presentation. These episodes are a recognized but infrequent feature of COQ8A disease, and the letter’s authors are careful to position their report within a small body of prior evidence. Hikmat and colleagues described ADCK3 mutations with epilepsy, stroke-like episodes and ataxia as far back as 2016, explicitly noting the resemblance to POLG-related mitochondrial disease, a better-known condition famous for its own stroke-like presentations. More recently, Ramesh and coworkers reported stroke-like episodes and epilepsy in a patient with COQ8A-related deficiency, and Radhakrishnan’s group documented young-onset ataxia-dystonia caused by the same gene. The recurrent posterior localization of the lesions in the present case adds a distinctive imaging dimension to this accumulating picture.

The mechanistic story behind stroke-like lesions in mitochondrial and energy-deficiency disorders is one of metabolic failure rather than vascular occlusion. In a true stroke, a blocked or ruptured blood vessel starves tissue of perfusion. In a stroke-like episode, the brain tissue itself fails, often triggered by metabolic stressors such as infection, seizures or the energy demands of normal neural activity, which become unsustainable when the electron transport chain cannot deliver sufficient ATP. Neurons in energy-hungry regions deplete their reserves, cytotoxic edema follows, and imaging shows lesions that can migrate, resolve and recur in a pattern that defies the fixed vascular territories of ischemic infarcts. This behavior is precisely what makes such lesions confusing, since the initial radiological read frequently favors stroke or PRES before the underlying metabolic cause is considered.

The stakes of this confusion are high for one crucial reason: COQ8A-related coenzyme Q10 deficiency is widely described in the literature as a potentially treatable genetic disease. High-dose oral coenzyme Q10 supplementation, when initiated early, can theoretically bypass the block in endogenous synthesis and restore some measure of electron transport function. Chang and colleagues made this point explicitly in 2018 in the journal Movement Disorders Clinical Practice, framing ADCK3-related deficiency as a treatable condition, and Mantle, Millichap, Castro-Marrero and Hargreaves updated the landscape of primary coenzyme Q10 deficiency in a 2023 review in Antioxidants. Treatment does not always reverse established neurological damage, and outcomes vary, but the contrast with the untreatable trajectories of many other ataxias makes an early, correct diagnosis transformative for patients and families.

The case also carries a sobering dimension that the authors handle with care. The patient described has died, and written informed consent for publication was obtained from the patient’s next of kin, with the case fully de-identified and identifying annotations removed from the images. The retrospective, anonymized account of the clinical course involved no intervention or deviation from standard care, and the Institutional Ethics Committee determined that formal ethical approval was not required under the Indian Council of Medical Research’s national ethical guidelines. The authors report no conflicts of interest and received no specific funding for the work. This transparency matters, because case reports that capture missed or delayed diagnoses often face reluctance to publish, and yet they are among the most educationally valuable contributions a clinical team can make.

From the perspective of the wider neurology community, the message is one of diagnostic vigilance. The authors and their supporting literature sketch a recognizable pattern: a patient presenting with what appears to be recurrent posterior circulation stroke or PRES, whose episodes recur atypically, whose imaging shows lesions that do not respect vascular territories or who develops progressive gait ataxia over time, should trigger consideration of a primary coenzyme Q10 deficiency. Confirming the diagnosis today rests on genetic testing of the COQ8A gene, alongside biochemical assessments of coenzyme Q10 status where available, and the expanding availability of affordable sequencing is steadily lowering the barrier to making this diagnosis in resource-limited settings, where such cases are often first encountered.

The broader significance of this letter extends beyond a single gene. It joins a growing catalogue of metabolic epilepsies and encephalopathies that masquerade as vascular emergencies, from POLG-related disease to lysinuric protein intolerance and beyond. Each such report sharpens the pattern recognition that emergency physicians, radiologists and neurologists bring to the initial hours of a patient’s care. A stroke-like lesion in a young patient with an unexplained progressive gait disorder is not merely a puzzle; it may be a metabolic alarm. In the case of COQ8A-related coenzyme Q10 deficiency, recognizing that alarm early and starting targeted supplementation represents one of the few genuine windows of intervention in the world of inherited ataxias, and every published account of the diagnostic path broadens that window for the next patient who arrives in an emergency department with lesions that look like strokes but are nothing of the kind.

Subject of Research: COQ8A-related coenzyme Q10 deficiency presenting as recurrent posterior stroke-like lesions

Article Title: Recurrent posterior stroke-like lesions heralding COQ8A-related coenzyme Q10 deficiency: a potentially treatable ataxia mistaken for stroke: a case report

Article References: Recurrent posterior stroke-like lesions heralding COQ8A-related coenzyme Q10 deficiency: a potentially treatable ataxia mistaken for stroke: a case report. (n.d.). https://doi.org/10.1007/s00415-026-14209-x

Image Credits: AI Generated

DOI: 10.1007/s00415-026-14209-x

Keywords: COQ8A, coenzyme Q10 deficiency, stroke-like episodes, cerebellar ataxia, mitochondrial disease, posterior reversible encephalopathy syndrome, genetic diagnosis, neurogenetics, ubiquinone, Journal of Neurology, ADCK3, treatable ataxia