What is the diagnosis and treatment for a patient with right hemifacial sweating and tingling sensation in bilateral upper and lower limb palms and soles?

Diagnosis: Harlequin Syndrome with Peripheral Neuropathy

This patient most likely has Harlequin syndrome (unilateral hemifacial hyperhidrosis) combined with a peripheral sensory neuropathy affecting the palms and soles, requiring MRI of the brain and cervical spine to exclude structural lesions, followed by autonomic testing and evaluation for small fiber neuropathy.

Clinical Diagnosis

Harlequin Syndrome Features

• Right hemifacial sweating represents compensatory hyperhidrosis in response to contralateral sympathetic dysfunction, typically manifesting as asymmetric facial flushing and sweating with contralateral anhidrosis 1, 2
• The unilateral hemifacial hyperhidrosis pattern is pathognomonic for Harlequin syndrome, which results from autonomic nervous system dysfunction affecting sudomotor and vasomotor pathways 1, 2
• This can be idiopathic (primary) with a benign course, or secondary to structural abnormalities including cervical disc herniation, brainstem lesions, or iatrogenic factors 2, 3

Peripheral Neuropathy Component

• Bilateral tingling in palms and soles indicates a distal symmetric sensory polyneuropathy (DSP), likely involving small fiber sensory nerves 4
• The combination of autonomic dysfunction (hemifacial sweating) with sensory symptoms suggests a small fiber sensory polyneuropathy (SFSN) affecting both autonomic and somatic C fibers concurrently 4
• This pattern differs from Ross syndrome (Harlequin + Adie pupils + areflexia), as preserved reflexes would exclude that diagnosis 1

Diagnostic Workup Algorithm

First-Line Imaging (Mandatory)

• Order MRI of the brain with and without contrast using thin-cut high-resolution sequences to evaluate the brainstem, facial nerve pathways, and exclude structural lesions such as infarction, vascular malformations, tumors, or multiple sclerosis 4
• Order MRI of the cervical spine to exclude cervical disc herniation causing myelopathy, as lateral compression can cause ipsilateral hemifacial hyperhidrosis while paramedian compression causes contralateral patterns 3
• Cervical disc herniation with lateral dural compression may influence circulation to the sudomotor pathway, while paramedian compression affects the ipsilateral sulcal artery perfusing the sympathetic descending pathway 3

Autonomic Testing (Essential)

• Perform a battery of validated autonomic tests to document autonomic nervous system dysfunction, particularly for suspected autonomic neuropathy and distal small fiber sensory polyneuropathy 4
• Include cardiovagal function testing (heart rate variability), adrenergic function assessment, and postganglionic sudomotor function testing to evaluate both parasympathetic and sympathetic autonomic function 4
• Conduct sweat function testing and thermography to confirm the pattern of hyperhidrosis and map the distribution of sudomotor dysfunction, determining whether hypohidrosis exists on the contralateral side 3

Small Fiber Neuropathy Evaluation

• Consider skin biopsy to determine intraepidermal nerve fiber (IENF) density for diagnosis of distal symmetric polyneuropathy, particularly small fiber sensory neuropathy affecting palms and soles 4
• Skin biopsy is a validated technique that may be considered for the diagnosis of DSP, especially when small fiber involvement is suspected 4

Laboratory Workup for Secondary Causes

• Screen for diabetes mellitus, vitamin B12 deficiency, thyroid dysfunction, autoimmune disorders, and other metabolic causes of peripheral neuropathy
• Consider testing for amyloidosis if nerve biopsy becomes necessary based on clinical progression 4

Treatment Approach

For Hemifacial Hyperhidrosis

• Topical glycopyrrolate is first-line treatment for craniofacial sweating 5
• Botulinum toxin injection (onabotulinumtoxinA) is considered first- or second-line treatment for craniofacial hyperhidrosis 5
• Oral anticholinergics are useful adjuncts in severe cases when other treatments fail 5
• If cervical disc herniation is identified, neurosurgical consultation for decompression should be considered, as this may resolve the hemifacial hyperhidrosis 3

For Peripheral Neuropathy (Palms and Soles Tingling)

• Treatment depends on the underlying etiology identified through diagnostic workup
• Address any reversible causes (diabetes control, vitamin supplementation, etc.)
• Symptomatic management with gabapentinoids or tricyclic antidepressants for neuropathic pain if present

Critical Pitfalls to Avoid

• Do not assume this is idiopathic Harlequin syndrome without excluding structural causes, particularly cervical myelopathy, brainstem lesions, or tumors that require specific intervention 2, 3
• Do not overlook the bilateral nature of the sensory symptoms – this suggests a systemic process (peripheral neuropathy) rather than a focal autonomic disorder alone 4
• Do not confuse this with hemifacial spasm, which presents with involuntary facial muscle contractions rather than sweating abnormalities 6, 7
• Hemifacial spasm is caused by vascular compression of the facial nerve and presents with facial twitching, not autonomic dysfunction 6
• Do not delay imaging if symptoms are progressive or associated with other neurological signs, as this could indicate serious underlying pathology requiring urgent intervention 4, 3