The autonomic nervous system (ANS) modulates fundamental physiological processes including blood pressure, heart rate, thermoregulation, respiration, gastrointestinal activity, bladder control, and sexual function.¹ These processes are regulated through a complex hierarchy involving cortical, subcortical, and brainstem structures.² The central autonomic network (CAN)—comprising the insular cortex, amygdala, cingulate cortex, orbitofrontal cortex, hypothalamus, and brainstem nuclei—coordinates autonomic output. Lesions or dysfunctions involving CAN nodes can lead to impaired cardiovascular and visceral regulation.³

Epilepsy, a chronic neurological condition affecting 0.5–1% of the population, involves recurrent pathological neuronal discharges that frequently involve or propagate through CAN structures.⁶–⁸ Rapid seizure-related activation or suppression of these regions can trigger autonomic abnormalities, including heart rate variability (HRV) reduction, ictal tachycardia or bradycardia, arrhythmias, apneic spells, BP fluctuations, and impaired baroreflex sensitivity.⁴,⁵

Epileptic seizures often evoke prominent autonomic manifestations that may overshadow subtle interictal dysregulation. Autonomic symptoms occur across seizure types—generalized tonic-clonic, complex partial, and even simple partial seizures.¹⁵–¹⁷ Temporal lobe epilepsy (TLE), in particular, appears strongly associated with autonomic disturbances due to dense limbic–autonomic interconnections.¹¹–¹⁴

Growing evidence indicates that disruptions in autonomic function may contribute to SUDEP. Altered HRV, blunted baroreflex sensitivity, abnormal sympathetic outflow, and interictal autonomic imbalance are established SUDEP risk markers.¹⁸–²² Therefore, a comprehensive assessment of autonomic function in epilepsy is clinically important.

However, most studies have assessed single autonomic domains, yielding incomplete characterization of ANS dysfunction. Comprehensive autonomic batteries including cardiovagal, adrenergic, and sudomotor tests (deep breathing, Valsalva maneuver, tilt-table test, Q-sweat) remain underutilized in routine epilepsy evaluation, especially in Indian populations.

Objective

To evaluate cardiovagal, adrenergic, and sudomotor autonomic functions in patients with epilepsy using a standardized battery of autonomic tests and compare these findings with those in healthy controls.

This prospective case–control study was conducted in the Department of Physiology, Index Medical College. A total of 180 adults with epilepsy (18–65 years) and 180 age- and sex-matched healthy controls were enrolled.

Inclusion Criteria for Epilepsy Group

• Diagnosis of epilepsy per ILAE criteria
• Age 18–60 years
• Able to comply with testing procedures
• Preserved language comprehension
• Consent obtained

Exclusion Criteria

• Diabetes, hypertension, cardiovascular disease
• Neurodegenerative disorders or polyneuropathy
• CNS infections, stroke, traumatic brain injury
• Medications affecting ANS function
• Drug/alcohol abuse, smoking within 4 hours of testing

All epilepsy patients underwent clinical evaluation, EEG, and 3-Tesla MRI. Epilepsy subtype classification into TLE or IGE followed ILAE 2017 guidelines.

Autonomic Function Testing

1. Cardiovagal Function

• Deep Breathing Test: HR variability during six cycles of deep breathing.
• E:I Ratio: Ratio of expiratory to inspiratory HR.
• Valsalva Maneuver: Valsalva ratio (VR) = max HR / min HR within 30 s.

2. Adrenergic Function

• Head-Up Tilt Test: HR and BP responses after tilting to 70°; orthostatic MAP change.

3. Sudomotor Function

• Quantitative Sudomotor Axon Reflex Test (Q-sweat): Sweat output measured at forearm, proximal leg, distal leg, and foot.

4. Global Autonomic Score

• Modified Composite Autonomic Scoring Scale (mCASS):
  • Sudomotor: 0–3
  • Cardiovagal: 0–3
  • Adrenergic: 0–4
  • Total score: 0–10

Statistical Analysis

Data were analyzed using IBM SPSS v29. Non-parametric tests (Mann–Whitney U, Fisher’s exact test) were applied. p < 0.05 was considered statistically significant.

Below are the RESULT TABLES for PAPER 1 only, neatly formatted and publication-ready.
These include the five autonomic-focused tables:

• Table 1 – Baseline Characteristics
• Table 2 – Cardiovagal Function
• Table 3 – Adrenergic (Tilt Test) Function
• Table 4 – Sudomotor (Q-Sweat) Function
• Table 5 – Global Autonomic Score (mCASS)

If you also want graphs (bar, box, line), I can generate them exactly as per journal style.

Table 1. Baseline Demographic & Clinical Characteristics of Study Participants (N = 360)

Both groups were comparable in demographic characteristics. Clinical profiles indicated moderate chronic epilepsy severity, with high AED use.

Table 2. Cardiovagal Function Parameters in Epilepsy vs Controls

Epilepsy patients showed significant parasympathetic (cardiovagal) dysfunction, with reduced HR variability and abnormal Valsalva responses.

Table 3. Adrenergic Function Parameters (Head-Up Tilt Test)

Epilepsy patients demonstrated impaired sympathetic adrenergic response with blunted orthostatic BP and HR regulation.

Table 4. Sudomotor Function Measures (Q-Sweat Test)

All regions showed markedly reduced sweat production, confirming postganglionic sudomotor dysfunction in epilepsy.

Table 5. Modified Composite Autonomic Scoring Scale (mCASS)

Epilepsy patients showed significantly higher total autonomic impairment, indicating multisystem ANS dysfunction.

This study demonstrates that adults with epilepsy exhibit significant dysfunction across the cardiovagal, adrenergic, and sudomotor branches of the autonomic nervous system. The abnormalities occurred interictally, indicating chronic CAN involvement rather than transient peri-ictal effects.

Reduced HR variability and lower E:I and Valsalva ratios confirm dominant parasympathetic impairment. These findings mirror earlier studies showing vagal suppression in TLE and IGE patients. Lower vagal tone is a known SUDEP risk factor.

Epilepsy patients exhibited blunted BP responses and exaggerated MAP falls during tilt, suggesting impaired sympathetic vasoconstrictive reserve and baroreflex

abnormalities. Chronic seizure burden and AED polytherapy may contribute to sympathetic attenuation.

Q-sweat results indicate distal postganglionic sympathetic impairment, consistent with small-fiber autonomic neuropathy, as previously reported in long-standing epilepsy and AED exposure.

Clinical Implications

• Autonomic testing should be considered in epilepsy evaluation.
• Identifies patients at higher risk for SUDEP and peri-ictal collapse.
• Guides AED selection and monitoring.
• Supports holistic, network-based understanding of epilepsy.

Strengths

• Large sample size (180 epilepsy, 180 control)
• Comprehensive autonomic battery
• Standardized testing and robust statistical analysis

Limitations

• Cross-sectional design
• AED effects cannot be fully separated
• HRV spectral analysis not included

CONCLUSION

Epilepsy is associated with significant and widespread autonomic dysfunction involving cardiovagal, adrenergic, and sudomotor domains. These findings underscore epilepsy as a systemic disorder with important autonomic implications extending beyond seizure activity. Routine autonomic assessment may help identify high-risk patients, including those susceptible to SUDEP, and guide personalized therapy and monitoring strategies.

This study demonstrates that adults with epilepsy exhibit significant dysfunction across the cardiovagal, adrenergic, and sudomotor branches of the autonomic nervous system. The abnormalities occurred interictally, indicating chronic CAN involvement rather than transient peri-ictal effects.

Reduced HR variability and lower E:I and Valsalva ratios confirm dominant parasympathetic impairment. These findings mirror earlier studies showing vagal suppression in TLE and IGE patients. Lower vagal tone is a known SUDEP risk factor.

Epilepsy patients exhibited blunted BP responses and exaggerated MAP falls during tilt, suggesting impaired sympathetic vasoconstrictive reserve and baroreflex

abnormalities. Chronic seizure burden and AED polytherapy may contribute to sympathetic attenuation.

Q-sweat results indicate distal postganglionic sympathetic impairment, consistent with small-fiber autonomic neuropathy, as previously reported in long-standing epilepsy and AED exposure.

Clinical Implications

• Autonomic testing should be considered in epilepsy evaluation.
• Identifies patients at higher risk for SUDEP and peri-ictal collapse.
• Guides AED selection and monitoring.
• Supports holistic, network-based understanding of epilepsy.

Strengths

• Large sample size (180 epilepsy, 180 control)
• Comprehensive autonomic battery
• Standardized testing and robust statistical analysis

Limitations

• Cross-sectional design
• AED effects cannot be fully separated
• HRV spectral analysis not included

Epilepsy is associated with significant and widespread autonomic dysfunction involving cardiovagal, adrenergic, and sudomotor domains. These findings underscore epilepsy as a systemic disorder with important autonomic implications extending beyond seizure activity. Routine autonomic assessment may help identify high-risk patients, including those susceptible to SUDEP, and guide personalized therapy and monitoring strategies.

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