Cheiro-Oral Syndrome

Key Points at a Glance

Highlights of This Disease

• Cheiro-oral syndrome (COS) is a rare neurological disorder presenting with sensory disturbances in the perioral area and ipsilateral hand and fingers.
• The close anatomical arrangement of the ventroposteromedial nucleus (VPM) and ventroposterolateral nucleus (VPL) of the thalamus is the anatomical basis for simultaneous symptoms in the mouth and hand.
• The majority of cases are caused by ischemic stroke, but tumors, subdural hematomas, aneurysms, and encephalitis can also be causes.
• Ischemia to structures near the thalamus may cause oculomotor disturbances and visual field defects to accompany COS.
• It may present episodically as a transient ischemic attack (TIA) and may occur without brain lesions.
• Head MRI, CT, and CT angiography are important for diagnosis, and treatment is based on the underlying cause.
• Appropriate management of vascular risk factors is most important for preventing future infarction.

1. What is Cheiro-Oral Syndrome?

Cheiro-Oral Syndrome (COS) is a rare neurological disorder presenting with sensory disturbances in the finger (cheiro) and perioral (oral) regions. It is classified as a rare subtype of thalamic stroke syndromes.

COS is classified into the following four classes based on the lesion site and symptom distribution.

Class I

Definition: Sensory disturbance contralateral to a lesion in the brainstem or thalamus.

Symptom distribution: Sensory disturbances in the face (around the mouth) and hands/fingers appear on the same side. This is the most typical form.

Class II

Definition: COS with bilateral sensory disturbances.

Symptom distribution: Bilateral sensory abnormalities in both the face and fingers.

Type III

Definition: Bilateral symptoms around the mouth and unilateral symptoms in the hands/fingers, or vice versa.

Symptom distribution: A complex pattern with asymmetry in the face and upper limbs.

Type IV

Definition: Crossed cheiro-oral syndrome (crossed COS).

Symptom distribution: Perioral symptoms on one side of the body and upper limb symptoms on the opposite side appear simultaneously.

In relation to ophthalmology, involvement of structures adjacent to the thalamus can cause efferent (ocular motility disorders) or afferent (vision loss) impairments to be associated with COS.

Q How rare is cheiro-oral syndrome?

A

It has been reported as a subtype of thalamic stroke syndrome, and its incidence is rare. Clear prevalence data are limited, but some stroke patients develop it as COS.

2. Main Symptoms and Clinical Findings

Subjective Symptoms

• Cheiro-oral sensory abnormality: Numbness and paresthesia around the mouth corner and on the ipsilateral hand/fingers are the main symptoms.
• Diplopia: Binocular double vision occurs when eye movement disorders are present.
• Transient episodes: When appearing as TIA, symptoms may present as transient recurrent episodes lasting less than 60 minutes.

Toudou-Daouda et al. (2024) reported a 52-year-old man who experienced three transient recurrent episodes lasting less than 60 minutes, presenting with left hand paresthesia and binocular horizontal diplopia with esotropia ¹⁾. The cause was sub-occlusive right carotid bulb atherosclerotic stenosis, and neurological examinations between episodes were normal.

Clinical Findings

• Decreased pain and discriminative touch sensation: Reduced pin-prick pain sensation and discriminative touch around the mouth and fingers.
• Ocular motility disorders: Findings depend on the location of the associated lesion.

The following shows ocular motor and visual pathway disturbances related to lesion location.

Lesion Location	Clinical Features
Midbrain, medial longitudinal fasciculus (MLF)	Internuclear ophthalmoplegia (INO)
Midbrain tegmentum	Nystagmus or oculomotor nerve palsy
Posterior to optic chiasm	Homonymous hemianopia

• Findings due to optic tract lesions: May cause complete or incomplete incongruous homonymous hemianopia, a characteristic pattern of optic disc pallor, and a relative afferent pupillary defect (RAPD).

Q Why do eye symptoms occur in hand-mouth syndrome?

A

Ischemia to structures adjacent to the thalamus can cause multiple ophthalmic complications. Internuclear ophthalmoplegia (medial longitudinal fasciculus lesion), nystagmus/oculomotor nerve palsy (midbrain tegmentum lesion), and homonymous hemianopia (postchiasmal lesion) are typical. In optic tract lesions, because pupillary motor fibers cross unevenly at the chiasm and travel through the optic tract before branching at the brachium of the superior colliculus, RAPD may appear.

3. Causes and Risk Factors

The main causes of COS are as follows.

• Ischemic stroke: The most common cause. Infarction in the territory of perforating arteries of the thalamus and brainstem is typical.
• Hemorrhagic stroke: Caused by thalamic hemorrhage, etc.
• Tumor: Neoplastic lesions in the thalamus and brainstem region.
• Subdural hematoma: Compresses the thalamus and brainstem due to mass effect.
• Aneurysm: Nerve damage due to compression or hemorrhage.
• Encephalitis: Sensory disturbances due to inflammatory lesions.
• Extracranial internal carotid artery (ICA) atherosclerotic stenosis: May cause COS without brain lesions¹⁾.

Vascular risk factors include ischemic heart disease, hyperlipidemia, hypertension, diabetes, and smoking.

Prevention and Daily Care

Smoking, hypertension, diabetes, and hyperlipidemia are major risk factors for stroke, including COS. Continuing smoking cessation and appropriate management of blood pressure, blood sugar, and lipids is most important for preventing future cerebrovascular events. If you experience transient numbness or double vision, seek medical attention immediately.

Q Can hand-mouth syndrome occur without stroke?

A

Stroke is the most common cause, but tumors, subdural hematomas, aneurysms, and encephalitis can also be causes. Furthermore, it has been reported that COS can occur without brain parenchymal lesions even with extracranial ICA stenosis (atherosclerosis, arterial dissection)¹⁾.

4. Diagnosis and Examination Methods

When COS is suspected, detailed examination centered on neuroimaging is necessary.

• Head CT: Detects acute ischemic infarction, hemorrhage, and structural lesions of the thalamus (low-density areas). Useful for emergency evaluation.
• CT angiography (CTA): Rapidly evaluates large vessel occlusion. Also effective for detecting medium and small vessel occlusion. Used to detect atherosclerotic stenosis of the carotid bulb ¹⁾.
• Head MRI: Used for definitive diagnosis of ischemia and other lesions causing COS. Diffusion-weighted imaging (DWI) has high sensitivity and specificity for diagnosing acute stroke. Note that COS can occur even without brain lesions on MRI ¹⁾.

The characteristics of the main imaging methods are shown below.

Examination method	Main use	Characteristics
Head CT	Acute screening	Rapid evaluation of hemorrhage and acute infarction
CTA	Vascular assessment	Visualization of large vessel occlusion and carotid stenosis
Head MRI/DWI	Definitive diagnosis	High-sensitivity detection of acute ischemia and small infarcts

For COS due to ischemia, a complete stroke work-up is recommended. Routine blood tests (including complete blood count, biochemistry, and HbA1c) are also essential for evaluating vascular risk factors.

5. Standard Treatment

The basic principle of COS treatment is to address the underlying cause.

• Treatment of underlying disease: Identify the site and etiology of COS using neuroimaging, and treat the underlying cause.
• Management of vascular risk factors: Management of ischemic heart disease, hyperlipidemia, hypertension, diabetes, and smoking is paramount for preventing future infarction.
• Carotid endarterectomy: Indicated when severe carotid artery stenosis is the cause. In the case by Toudou-Daouda et al. (2024), no recurrence of cerebrovascular events was observed for one year after right carotid endarterectomy¹⁾.
• Antithrombotic therapy: Antiplatelet or anticoagulant drugs are used for secondary prevention of ischemic lesions.

The fact that the oculomotor nerves (III, IV, VI) run within the cavernous sinus and receive blood supply from branches of the ICA is an important anatomical background for determining treatment strategy. Since superior orbital fissure syndrome and cavernous sinus syndrome present with total ophthalmoplegia and sensory disturbance in the first division of the trigeminal nerve, attention must be paid to differentiation and possible coexistence.

Precautions in treatment

• COS often appears as a symptom of stroke, and even transient symptoms are dangerous if left untreated.
• Treatment strategies vary greatly depending on the underlying cause, so collaboration among neurologists, neurosurgeons, and ophthalmologists is important.
• When carotid artery stenosis is the cause, the indication for endarterectomy should be carefully evaluated on a case-by-case basis.

6. Pathophysiology and Detailed Mechanisms

Anatomical Background of the Sensory Homunculus

The anatomical basis for the simultaneous occurrence of sensory deficits around the mouth and in the ipsilateral upper limb is as follows.

• Proximity of nuclei in the thalamus: The ventral posteromedial nucleus (VPM: facial and oral sensation) and ventral posterolateral nucleus (VPL: trunk and limb sensation) of the thalamus, which relay sensory information, are closely adjacent.
• Proximity of sensory pathways in the brainstem: The spinothalamic tract (pain and temperature from trunk and limbs) and the trigeminothalamic tract (pain and temperature from the face) run close together.

Q Why do mouth and hand symptoms appear simultaneously?

A

This is because the VPM and VPL of the thalamus are anatomically close, so even a small lesion can easily affect both nuclei simultaneously. Similarly, in the brainstem, the spinothalamic tract and trigeminothalamic tract run close together.

Cortical COS

Cortical COS can also occur due to lesions of the sensory cortex in the postcentral gyrus. Chen WH et al. (2006) reexamined the clinical significance and etiology of cortical COS and reported cortical COS caused by postcentral gyrus lesions⁵⁾.

Pathophysiology of abducens nerve palsy (relationship with ICA stenosis)

In the case reported by Toudou-Daouda et al. (2024), the mechanism was estimated as severe stenosis of the right carotid bulb → decreased blood flow in the cavernous segment of the ICA → hypoperfusion of the lateral trunk (arterial trunk supplying the ocular motor nerves) → ischemia of the abducens nerve ¹⁾. Tekdemir et al. (1998) anatomically demonstrated that the abducens nerve receives blood supply from ICA branches within the cavernous sinus ⁴⁾.

Usually, the combination of brainstem ocular motor disorder and COS suggests a lesion in the posterior circulation (pons/thalamus), but it is clinically important that the same syndrome can also occur with extracranial lesions of the anterior circulation (ICA) ¹⁾.

Blood supply of ocular motor nerves

The oculomotor, trochlear, and abducens nerves receive blood supply from branches of the basilar artery, superior cerebellar artery, and anterior inferior cerebellar artery, respectively, in their cisternal segments ³⁾. In spontaneous occlusive dissection of the ICA, isolated oculomotor nerve palsy can occur due to embolism to the arterial trunk supplying the oculomotor nerve, hemodynamic mechanisms, or both ²⁾.

Mechanism of optic tract lesions

In optic tract lesions, contralateral homonymous hemianopia occurs. Damage to parent vessels including the basilar artery, posterior cerebral artery, and posterior communicating artery causes optic tract abnormalities. Since pupillary motor fibers cross unevenly at the optic chiasm and run through the optic tract before branching at the superior colliculus brachium, optic tract lesions can cause a relative afferent pupillary defect (RAPD).

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7. Latest Research and Future Perspectives (Reports under Investigation)

For Patients: Please Read Carefully

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

First Report of Oculomotor Nerve Palsy Due to Carotid Artery Stenosis

Toudou-Daouda et al. (2024) reported the world’s first case of transient abducens nerve palsy due to atherosclerotic stenosis of the carotid bulb (without brain lesions)¹⁾. In this case, abducens nerve palsy and COS coexisted as recurrent TIAs, and no recurrence was observed for one year after carotid endarterectomy.

This report highlights the importance of evaluating extracranial ICA stenotic disease (arterial dissection or atherosclerosis) in patients presenting with acute permanent or transient ocular motor nerve palsy.

Prognostic Findings

According to one report, only 14 of 85 patients (16.5%) showed worsening or progression of symptoms in the acute phase. Patients with subcortical lesions often have a good prognosis. Lesions due to subdural hematoma or brainstem infarction are associated with a poorer prognosis.

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8. References

1. Toudou-Daouda M, Yatwa-Zaniwe RV, Aminou-Tassiou NR, Chausson N, Smadja D. Transient recurrent episodes of abducens nerve palsy and cheiro-oral syndrome in a sub-occlusive carotid bulb atherosclerotic stenosis. Oxford Medical Case Reports. 2024;2024(3):113–115. doi:10.1093/omcr/omae020.

2. Campos CR, Massaro AR, Scaff M. Isolated oculomotor nerve palsy in spontaneous internal carotid artery dissection: case report. Arquivos de neuro-psiquiatria. 2003;61(3A):668-70. doi:10.1590/s0004-282x2003000400027. PMID:14513178.

3. Mercier P, Brassier G, Fournier HD, Delion M, Papon X, Lasjaunias P. [Morphological anatomy of the cranial nerves in their cisternal segment (III-XII)]. Neuro-Chirurgie. 2009;55(2):78-86. doi:10.1016/j.neuchi.2009.01.019. PMID:19328500.

4. Tekdemir I, Tüccar E, Cubuk HE, Ersoy M, Elhan A, Deda H. Branches of the intracavernous internal carotid artery and the blood supply of the intracavernous cranial nerves. Annals of anatomy = Anatomischer Anzeiger : official organ of the Anatomische Gesellschaft. 1998;180(4):343-8. doi:10.1016/S0940-9602(98)80040-X. PMID:9728276.

5. Chen WH, Lan MY, Chang YY, Lui CC, Chen SS, Liu JS. Cortical cheiro-oral syndrome: a revisit of clinical significance and pathogenesis. Clinical neurology and neurosurgery. 2006;108(5):446-50. doi:10.1016/j.clineuro.2005.07.007. PMID:16139420.