Fluctuating Arousal Failure with Repeatedly Negative DWI Preceding Artery of Percheron Infarction: A Case Report and Focused Literature Review

Technical Summary: Fluctuating Arousal Failure with Repeatedly Negative DWI Preceding Artery of Percheron Infarction

Problem Statement
Artery of Percheron (AoP) infarction is a rare subtype of posterior-circulation stroke resulting from the occlusion of a solitary thalamoperforating artery supplying the bilateral paramedian thalami and often the rostral midbrain. A critical diagnostic challenge lies in the heterogeneity of its early presentation and the limited sensitivity of diffusion-weighted imaging (DWI) in the hyperacute phase, particularly for small posterior perforator infarctions. Consequently, patients may present with recurrent, transient neurological deficits that mimic posterior-circulation transient ischemic attacks (TIAs), syncope, or metabolic encephalopathy. The clinical dilemma is whether to proceed with acute reperfusion therapy when early neuroimaging (specifically DWI) is negative, despite a coherent and disabling clinical syndrome localized to the posterior circulation.

Methodology
This study presents a single case report of a 65-year-old male adhering to CARE (CAse REport) guidelines. The methodology involves a comprehensive retrospective analysis of the patient's clinical course, neuroimaging, and therapeutic interventions.

• Clinical Assessment: The patient presented with recurrent, brief episodes (3–10 minutes) of impaired arousal (Glasgow Coma Scale score of 6 during attacks) accompanied by binocular diplopia and transient ocular deviation. Detailed neurological examinations were performed during and between episodes to localize lesions to the brainstem and thalamic networks.
• Diagnostic Imaging: The patient underwent emergency non-contrast CT, CT angiography (CTA), and serial MRI scans. Initial MRI was performed approximately 3 hours post-onset, with a repeat MRI within 24 hours. A follow-up MRI was conducted on hospital day 5.
• Therapeutic Intervention: Based on the clinical localization of posterior-circulation ischemia and the exclusion of hemorrhage, the patient received intravenous Tenecteplase (0.25 mg/kg) within the therapeutic window (door-to-needle time: 58 minutes). Subsequent management included antiplatelet therapy, statins, and treatment for hyperhomocysteinemia.
• Differential Diagnosis: The authors systematically evaluated potential mimics, including brainstem epilepsy, Wernicke encephalopathy, metabolic/toxic encephalopathy, and demyelinating disease, using clinical features and diagnostic test results (EEG, laboratory panels) to rule them out.

Key Results

• Clinical Presentation: The patient exhibited a distinct pattern of fluctuating arousal failure interspersed with complete interictal recovery and amnesia. Key focal signs included right internuclear ophthalmoplegia (INO), which localized the lesion to the medial longitudinal fasciculus (MLF) and the ascending reticular activating system (ARAS).
• Imaging Evolution: Both the initial MRI (3 hours post-onset) and the repeat MRI (within 24 hours) were DWI-negative, showing no acute restricted diffusion. This persisted despite the patient's disabling symptoms.
• Therapeutic Outcome: Following thrombolysis and antithrombotic management, the patient's condition evolved from transient episodes to persistent deficits. On hospital day 5, MRI revealed acute infarction of the bilateral paramedian thalami and rostral midbrain, confirming the diagnosis of AoP infarction.
• Long-term Status: By discharge (day 22), the patient's level of arousal had improved, but he retained residual diplopia, anisocoria, ptosis, oculomotor dysfunction, and cognitive impairment (MMSE 23/30, MoCA 19/30).

Key Contributions

1. Phenotypic Characterization: The report documents that AoP infarction can initially manifest as recurrent, short-lived arousal failure with focal ocular motor signs, closely mimicking posterior-circulation TIAs rather than presenting as immediate fixed coma.
2. Diagnostic Localization: The study emphasizes that coherent bedside neuroanatomical localization (specifically the combination of ARAS disruption and INO) is diagnostically decisive. These signs point to the rostral brainstem/paramedian thalamic network even before imaging becomes positive.
3. Imaging Limitations: The case reinforces literature indicating that false-negative DWI is not uncommon in the first 24 hours of vertebrobasilar strokes. The authors demonstrate that a normal early DWI should not exclude acute ischemic stroke when the clinical syndrome is disabling and anatomically consistent.
4. Therapeutic Decision-Making: The report details the rationale for administering intravenous thrombolysis (Tenecteplase) based on clinical suspicion of evolving posterior-circulation ischemia despite negative initial imaging, highlighting that treatment decisions should prioritize the disabling nature of the clinical syndrome over initial negative imaging in this specific context.

Significance and Claims
The paper claims that AoP infarction may present as a "dynamic" syndrome of fluctuating arousal failure with repeatedly negative early DWI. The authors assert that in cases of suspected posterior perforator ischemia, dynamic neurological localization and serial MRI are essential. They conclude that a normal early DWI scan should not override a coherent, disabling posterior-circulation stroke syndrome or delay appropriate acute management.

The authors maintain a modest tone regarding therapeutic efficacy, explicitly stating that this single case cannot establish the efficacy of thrombolysis in preventing or causing specific outcomes, nor can it prove that the treatment prevented the progression to infarction. Instead, the significance lies in the diagnostic lesson: clinicians should not be dissuaded from treating disabling posterior-circulation strokes solely based on an initially normal DWI if the clinical localization is compelling.