Neuro-ophthalmologic signs of thalamic disorders

Key Points at a Glance

Highlights of This Disease

• Thalamic lesions cause various neuro-ophthalmic signs such as vertical gaze palsy, skew deviation, convergence disorder, pupillary abnormalities, and nystagmus.
• The most common etiology is hemorrhagic or ischemic vascular disorder, with hypertension, diabetes, and smoking as major risk factors.
• Bilateral thalamic infarction is rare, accounting for 0.6% of all first-ever ischemic strokes, and occlusion of the artery of Percheron is one of its main causes.
• Unilateral lesions often result in limited upward gaze palsy, but bilateral lesions cause more severe vertical gaze palsy, convergence abnormalities, and impaired consciousness.
• Initial CT scans are often normal; diffusion-weighted MRI (DWI) is essential for acute diagnosis.
• Treatment is based on acute management of the underlying cause; thrombolytic therapy may be indicated for ischemic stroke.

1. Neuro-Ophthalmic Manifestations of Thalamic Disease

Neuro-Ophthalmic Manifestations of Thalamic Disease refer to a variety of eye movement disorders, pupillary abnormalities, and eyelid abnormalities caused by thalamic lesions. The thalamus is a major relay station connecting the cortex and brainstem, and is involved in pathways to the vestibular system, frontal eye fields, and posterior parietal cortex. Damage to this area most commonly presents as vertical gaze palsy, but may also include skew deviation, convergence insufficiency, oculomotor nerve palsy, nystagmus, saccadic disorders, and smooth pursuit abnormalities.

Epidemiology

• Bilateral thalamic infarction: A rare condition accounting for approximately 0.6% of all first-time ischemic strokes⁶⁾
• Artery of Percheron infarction: Accounts for 0.1–2% of all ischemic strokes and 4–35% of all thalamic strokes²⁾
• Prevalence of the artery of Percheron: Reported in 11.7–33% of autopsy studies⁵⁾
• Mortality of artery of Percheron infarction: 12%⁵⁾

History

In 1973, French neurologist Gerard Percheron first reported cases presenting a unique pattern of bilateral thalamic infarction¹⁾. Since then, only a few hundred cases have been reported in the literature, and it is recognized as a rare but clinically important condition.

Q What is the Percheron artery? How is it different from normal blood vessels?

A

The Percheron artery is an anatomical variant where a single perforating branch arises from the P1 segment of the posterior cerebral artery and supplies both thalami and the rostral midbrain. Normally, independent perforating branches from each P1 supply one side each, but in the Percheron artery, a single vessel supplies both sides, so occlusion leads to bilateral thalamic infarction. It is reported to be present in 11.7–33% of the population⁵⁾.

2. Main symptoms and clinical findings

Subjective symptoms

• Sudden confusion, dysarthria, unilateral weakness: Common symptoms in the acute phase¹⁾
• Excessive drowsiness, decreased level of consciousness: In paramedian thalamic infarction, patients initially have difficulty waking up, with a tendency for the level of arousal to improve after a few days⁴⁾⁵⁾
• Diplopia: may be horizontal or vertical
• Peduncular hallucinosis: vivid, colorful visual hallucinations occurring after thalamic or midbrain infarction. First reported by Lhermitte in 1922. In a review of 85 cases by Galetta et al., 43/85 were due to ischemic infarction, and most resolved spontaneously within 3 days of onset³⁾
• Agitation and self-injurious behavior: reported as a rare symptom associated with thalamic hemorrhage⁹⁾

Clinical Findings (Findings Confirmed by Physician Examination)

Four Major Acute Signs of Percheron Artery Infarction

The following four findings have been reported as major acute signs of Percheron artery infarction⁵⁾.

Finding	Frequency
Vertical gaze palsy	65%
Memory impairment	58%
Confusion	53%
Coma	42%

Comparison of unilateral and bilateral lesions

Unilateral lesion

Upward gaze palsy: The most common finding.

Sensory disturbance: Lateral thalamic infarction may present with pure sensory disturbance.

Bilateral Lesions

Vertical gaze palsy: Upward, downward, or combined types may occur.

Convergence abnormality: Convergence insufficiency or convergence spasm.

Bilateral internuclear ophthalmoplegia (INO): Appears in cases with midbrain extension.

Oculomotor nerve palsy: Accompanied by pupillary abnormalities and ptosis during brainstem progression.

Ophthalmologic deficits corresponding to the location of thalamic lesions

Lesion location	Ophthalmologic deficit
Paramedian region	Convergence insufficiency
Dorsomedial nucleus	Loss of saccadic activity
Lamellar periventricular region	Loss of smooth pursuit eye movements
Caudal region	Pseudo-abducens palsy (thalamic esotropia)
Inferolateral region	Hypermetric saccades
Posterolateral region	Ipsilateral Horner syndrome
Dorsal region	Horizontal or vertical diplopia

Details of Vertical Gaze Palsy

The vertical brainstem gaze centers are the rostral interstitial nucleus of the medial longitudinal fasciculus (riMLF) and the interstitial nucleus of Cajal (INC), located in the pretectal region of the midbrain. Vertical gaze palsy occurs with thalamic or midbrain lesions, with upward gaze palsy being more common. Isolated downward gaze palsy is rare, but in progressive supranuclear palsy, downward gaze palsy often appears early.

Parinaud Syndrome (Dorsal Midbrain Syndrome)

The following symptoms appear with lesions near the cerebral aqueduct in the pretectal region.

• Upward gaze palsy: impairment of saccadic eye movements is more severe than that of smooth pursuit
• Convergence palsy
• Light-near dissociation
• Convergence-retraction nystagmus
• Skew deviation
• Collier sign (lid retraction)

Causes include noncommunicating obstructive hydrocephalus in infants, tumors (pineal tumor is typical) in young people, and vascular lesions in adults.

Skew deviation

Vertical strabismus due to supranuclear input abnormalities to the ocular motor neurons is called skew deviation. It occurs with otolithic lesions from the peripheral labyrinth to the lower brainstem and midbrain. It is differentiated by the direction of intorsion of the elevating eye: skew deviation shows intorsion, while superior oblique palsy shows extorsion. Unilateral lesions of the interstitial nucleus of Cajal (INC) cause an ocular tilt reaction (OTR) to the contralateral side.

Tectal pupil

Tectal pupil occurs due to damage to the pupillary light reflex pathway in the pretectal area or posterior commissure from dorsal midbrain lesions. The light reflex is absent, and the pupil size initially remains unchanged but gradually becomes moderately dilated bilaterally. The near reflex pathway runs more ventrally than the light reflex pathway and is less affected, resulting in light-near dissociation.

Other findings

• Bilateral miosis (pinhole pupil): A characteristic finding of thalamic hemorrhage. Accompanied by fixed midline position of the eyes⁵⁾
• Anisocoria + bilateral horizontal nystagmus: Reported in thalamic infarction⁶⁾
• Convergence-retraction nystagmus: Appears during upward gaze in thalamic midbrain infarction¹⁰⁾
• See-saw nystagmus: Reported in lesions of the diencephalon and the interstitial nucleus of Cajal¹⁰⁾

Q Can hallucinations occur in thalamic stroke?

A

Peduncular hallucinosis is a vivid, colorful visual hallucination that occurs after thalamic or midbrain infarction, and may include distorted images of animals or people. In most cases, it resolves spontaneously within 3 days without medication³⁾. Suspect this when new hallucinations appear in a stroke patient with no history of psychiatric illness.

3. Causes and Risk Factors

Etiology

The most common cause of acute thalamic lesions is hemorrhagic or ischemic vascular disorders. Other reported causes include:

• Migraine
• Metabolic: Thiamine deficiency (Wernicke encephalopathy)
• Inflammatory: Cerebral lupus
• Infectious: Bacterial abscess, cerebral syphilitic gumma
• Traumatic
• Neoplastic: Tumors and cysts
• Iatrogenic: Deep brain stimulation

Risk factors

• Arterial: Hypertension, diabetes, smoking, dyslipidemia¹⁾⁶⁾
• Venous thrombotic: Anemia, pregnancy, oral contraceptives, COVID-19 vaccination⁷⁾
• Intracerebral hemorrhage: Hypertension accounts for the majority

Bilateral thalamic lesions to differentiate

Diseases that cause bilateral thalamic lesions include not only Percheron artery infarction but also the following conditions to differentiate ⁷⁾.

• Deep cerebral vein thrombosis: Thrombosis of the internal cerebral vein, great vein of Galen, and straight sinus
• Viral encephalitis: WNV encephalitis, Japanese encephalitis
• Wernicke encephalopathy: Thiamine deficiency. T2 hyperintensity in the medial thalamus and mammillary bodies
• Wilson disease: Copper accumulation. T2 hyperintensity in the putamen, globus pallidus, caudate nucleus, and thalamus
• Tumors: glioma, neurocytoma, germ cell tumor

Prevention and Daily Care

The most common cause of thalamic lesions is cerebrovascular disease, and management of vascular risk factors is important for prevention. Continue treatment for hypertension, diabetes, and dyslipidemia, and aim to quit smoking. If sudden double vision, abnormal eye movements, or altered consciousness occur, seek medical attention promptly.

4. Diagnosis and Testing Methods

Imaging Diagnosis

Diagnosis of acute thalamic lesions primarily relies on imaging studies.

Examination method	Characteristics	Main uses
Plain CT	Differentiates hemorrhage/ischemia. Often normal on first scan	Acute phase screening
MRI DWI	Highest sensitivity and specificity	Definitive diagnosis of acute infarction
Magnetic resonance angiography (MRA)	Can visualize the Percheron artery	Evaluation of vascular lesions

Limitations of CT

In acute thalamic infarction, the initial CT is often normal. Multiple reports have shown that findings are absent on initial CT, and infarction is only confirmed on CT or MRI several days later¹⁾²⁾⁴⁾. In the case of Satei et al., bilateral thalamic infarction was finally depicted on the third CT scan⁵⁾.

Usefulness of MRI

Diffusion-weighted imaging (DWI) is the most excellent method for detecting acute thalamic ischemia¹⁾. FLAIR images depict cerebral infarction as hyperintense areas and cerebrospinal fluid as hypointense areas, making them useful for distinguishing between the two. In the hyperacute phase (within 6 hours of onset), lesion detection on T1/T2/FLAIR images may be difficult, and combined use of DWI is recommended.

V sign

In 67% of Percheron artery infarctions, a V-shaped hyperintense area (V sign) is observed on the surface of the midbrain on axial DWI or FLAIR images⁵⁾.

Imaging Findings of Deep Cerebral Venous Thrombosis

Non-contrast CT shows linear hyperdensity in the region of the internal cerebral vein, vein of Galen, and straight sinus, with diffuse hypodensity in both thalami (disappearing thalami). MRV confirms absence of flow in the deep venous system ⁷⁾.

Q Why is thalamic stroke sometimes not detected on the initial CT scan?

A

Thalamic infarction often results from occlusion of small perforating arteries, making it difficult to visualize on initial CT. If CT is negative but stroke is clinically suspected, adding MRI diffusion-weighted imaging (DWI) improves diagnostic sensitivity ¹⁾. Re-evaluation should be considered when there is a discrepancy between clinical and imaging findings.

5. Standard Treatment

Acute Phase Treatment (Ischemic Thalamic Infarction)

Thrombolytic therapy is indicated for acute ischemic thalamic infarction within 4.5 hours of onset. In Japan, alteplase, a recombinant tissue-type plasminogen activator (t-PA), is administered intravenously at a dose of 0.6 mg/kg. If recanalization is not achieved with intravenous t-PA, endovascular treatment using a stent retriever device is considered.

For Percheron artery infarction, thrombectomy within 6 hours of onset is an option in addition to tPA administration. In cases with midbrain involvement, intravenous heparin may be considered ²⁾.

Antiplatelet and Lipid Management

Aspirin is started 72 hours or more after thrombolytic therapy ¹⁾. Depending on the etiology, combination with clopidogrel 75 mg/day or switching to ticagrelor may be performed ³⁾⁶⁾. Lipid management with statins (e.g., atorvastatin 80 mg) and antihypertensive therapy (target 120/80–140/90 mmHg) are also carried out concurrently ¹⁾.

Anticoagulation Therapy for Venous Thrombosis

Arterial Infarction

Acute phase: Alteplase 0.6 mg/kg (within 4.5 hours)

Maintenance phase: Aspirin + statin. Selection of antiplatelet drug based on etiology

Venous infarction

Acute phase: Low molecular weight heparin (enoxaparin)

Maintenance phase: Oral anticoagulant (e.g., dabigatran) for 3–12 months⁷⁾

Treatment for ocular motor disorders

• Skew deviation: Often resolves or disappears with treatment of the underlying disease. For persistent cases, consider prism glasses or botulinum toxin injection. For fixed, permanent cases, vertical strabismus surgery may be applied.
• Peduncular hallucinosis: Usually resolves spontaneously within 2–3 days, and antipsychotics are not required³⁾.
• Behavioral abnormalities associated with thalamic hemorrhage: There are reports that oral haloperidol plus olanzapine 10 mg/day is effective⁹⁾.

VITT (Vaccine-Induced Immune Thrombotic Thrombocytopenia)

If VITT is suspected, start treatment with anticoagulants other than heparin and administer high-dose intravenous immunoglobulin (IVIG) 1 g/kg/day for 2 days⁶⁾. Plasma exchange is also an option.

Precautions and side effects in treatment

In acute thalamic infarction, even if the initial CT is normal, if stroke is strongly suspected clinically, MRI should be promptly added to prevent delays in starting treatment. Thrombolytic therapy is indicated only when hemorrhagic stroke has been ruled out, and time constraints (within 4.5 hours) must be strictly observed. When VITT is a differential diagnosis, caution is needed with heparin use.

Q Do eye symptoms of thalamic stroke improve?

A

Treatment of the underlying disease often improves eye movement disorders. Vertical gaze palsy and impaired consciousness due to paramedian thalamic infarction tend to recover gradually after the acute phase. For persistent skew deviation, prism glasses, botulinum toxin injection, or surgery may be indicated. However, sequelae may remain in elderly patients or those with extensive infarction.

6. Pathophysiology and Detailed Mechanisms

Vascular Supply of the Thalamus

The thalamus receives blood supply from several arterial branches.

• Thalamotuberal artery: Arises from the posterior communicating artery and supplies the anterior nucleus, ventral part of the dorsomedial nucleus, and rostral ventral lateral nucleus. In about one-third of the population, this artery is absent, and its territory is supplied by the paramedian artery ⁵⁾
• Paramedian artery: Supplies the dorsomedial part of the thalamus and the paramedian part of the midbrain
• Inferolateral arteries: Supply most of the ventral lateral nucleus, the pulvinar, and the ventral posterior nucleus
• Posterior choroidal arteries: Supply the dorsolateral part of the thalamus, substantia nigra, pulvinar, and lateral and medial geniculate bodies

Percheron artery and infarction patterns

The Percheron artery is a single perforating branch arising from the P1 segment, supplying the bilateral paramedian thalamus and part of the rostral midbrain ²⁾⁵⁾. The ischemic patterns upon occlusion are classified into the following four types ⁵⁾.

• Bilateral paramedian thalamus + midbrain (43%)
• Bilateral paramedian thalamus only (38%)
• Bilateral paramedian thalamus + anterior thalamus + midbrain (14%)
• Bilateral paramedian thalamus + anterior thalamus (5%)

When the midbrain is involved, hemiplegia, ataxia, and ocular movement disorders may occur.

Neural circuits of eye movement

The vertical eye movement center is located in the midbrain and involves the following nuclei and pathways.

• Rostral interstitial nucleus of the medial longitudinal fasciculus (riMLF): Contains burst neurons for vertical saccades. Upward gaze signals are transmitted from the riMLF via the posterior commissure (PC) to the bilateral oculomotor nuclei. Downward gaze signals reach the ipsilateral oculomotor and trochlear nuclei from the riMLF.
• Interstitial nucleus of Cajal (INC): Involved in vertical gaze holding.
• Posterior commissure (PC): Responsible for bilateral transmission of upward gaze signals. A PC lesion causes bilateral upward gaze palsy.

A unilateral riMLF lesion alone does not cause upward gaze palsy (because bilateral transmission via the PC is preserved). In contrast, bilateral riMLF lesions are required for bilateral downward gaze palsy.

Thalamic reticular nucleus (TRN) and mechanism of hypersomnia

90% of neurons in the thalamic reticular nucleus (TRN) are GABAergic (inhibitory) and are involved in gating thalamocortical information transmission and sleep regulation. When a TRN infarction occurs, sudden neuronal death causes massive GABA release, which is thought to contribute to hypersomnia ⁸⁾. Animal experiments have shown that TRN stimulation by cholinergic fibers promotes sleep.

Mechanism of Deep Cerebral Venous Sinus Thrombosis

When venous return is impaired due to thrombosis of the internal cerebral veins, great vein of Galen, and straight sinus, congestive edema occurs in the bilateral thalami, which can progress to infarction ⁷⁾. Unlike arterial occlusion, venous infarction is preceded by edema and is more likely to involve hemorrhagic changes.

Vascular Supply of the Lateral Geniculate Body and Visual Field Patterns

The lateral geniculate body (LGB) receives dual blood supply from the anterior choroidal artery (AchoA) and the lateral posterior choroidal artery (LPchoA), but these do not anastomose within the nucleus. LPchoA infarction damages the hilum of the LGB, resulting in homonymous horizontal sectoranopia, while distal AchoA infarction damages the medial and lateral parts of the LGB, causing quadruple sectoranopia. Occlusion of the main trunk of the posterior cerebral artery causes homonymous hemianopia combined with thalamic syndrome (contralateral sensory disturbance).

---

7. Latest Research and Future Prospects (Research-Stage Reports)

For Patients: Please Read Carefully

The following content is currently at the research stage or under clinical trial and is not standard treatment available at general hospitals. It is reference information for professionals regarding future medical developments.

Diagnostic Challenges of Percheron Artery Infarction

There are three major barriers to diagnosing Percheron artery infarction⁵⁾.

• Lack of knowledge: Low awareness of this arterial variant and its occlusion syndrome
• Imaging limitations: Initial CT often shows no findings
• Difficulty obtaining history due to lethargy: Deep drowsiness makes it hard to obtain information from the patient

Satei et al. (2021) reported a case of Percheron artery infarction in a 90-year-old man. The first and second CT scans were normal, and bilateral thalamic infarction was finally confirmed on the third CT scan several days after admission. The attending physician had initially considered transitioning to end-of-life care ⁵⁾.

In another case report, ischemic findings were first detected on CT 24 days after admission, and the patient died shortly thereafter ⁵⁾.

VITT (Vaccine-Induced Immune Thrombotic Thrombocytopenia) Research

VITT is a rare immune-mediated thrombosis reported with adenovirus vector vaccines (AstraZeneca, Janssen), with an estimated incidence of about 1 in 533,333 in the United States ⁶⁾.

Giovane et al. (2021) reported a 62-year-old man who developed bilateral thalamic infarction the day after COVID-19 vaccination. PF4 antibody ELISA was negative, and they concluded it was a coincidental occurrence with multiple risk factors including hypertension, diabetes, dyslipidemia, and end-stage renal disease⁶⁾.

Female sex and age under 60 have been reported as risk factors, but the number of cases is limited and not definitive. A systematic review is awaited.

TRN Research and Optogenetics

Kong et al. (2022) reported a 68-year-old woman who presented with hypersomnia due to TRN infarction. She received intravenous thrombolysis with urokinase 100 U and was treated with dl-NBP plus edaravone. Right lower limb muscle weakness improved, but hypersomnia persisted for 3 days⁸⁾.

Animal studies have shown that selective stimulation of TRN cholinergic fibers using optogenetic techniques prolongs non-REM sleep. It has also been suggested that massive GABA release during infarction may have neuroprotective effects, but clinical application has not been achieved⁸⁾.

---

8. References

1. Alaithan TM, Almaramhi HM, Felemban AS, et al. Artery of Percheron infarction: a rare but important cause of bilateral thalamic stroke. Cureus. 2023;15(4):e37054.

2. Shams A, Hussaini SA, Ata F, et al. Bilateral thalamic infarction secondary to thrombosis of artery of Percheron. Cureus. 2021;13(3):e13707.

3. Shahab M, Ahmed R, Kaur N, et al. Peduncular hallucinosis after a thalamic stroke. BMJ Case Rep. 2021;14:e241652.

4. Qureshi M, Qureshi M, Gul M, et al. Bilateral thalamic stroke as a cause of decreased responsiveness. Cureus. 2021;13(5):e14935.

5. Satei AM, Rehman CA, Munshi S. Bilateral thalamic stroke arising from an occlusion of the artery of Percheron: barriers to diagnosis, management, and recovery. Cureus. 2021;13(11):e19783.

6. Giovane R, Campbell J. Bilateral thalamic stroke: a case of COVID-19 vaccine-induced immune thrombotic thrombocytopenia (VITT) or a coincidence due to underlying risk factors? Cureus. 2021;13(10):e18977.

7. Sharma S, Dhakal P, Sharma A, et al. Deep venous sinus thrombosis with right thalamic infarction in a young patient after COVID-19 vaccination. Radiol Case Rep. 2022;17(9):3298-3301.

8. Kong W, Ma L, Yin C, et al. Unilateral thalamic infarction onset with lethargy: a case report and literature review. Medicine. 2022;101(48):e32158.

9. Sidow NO, Sheikh Hassan M. A case of autophagia with thalamic hemorrhage. Ann Med Surg. 2022;79:104030.

10. Gurnani B, et al. Nystagmus and abnormal eye movements review. Clin Ophthalmol. 2025;19:1617-1642.