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Diagnosed With FND, Her Tilt-Table Test Was Cancelled. Doctors Later Discovered Severe Autonomic Dysfunction

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A previously healthy 43-year-old woman became so severely ill during a COVID-19 infection that she could barely sit upright, let alone stand or walk. Her symptoms included dizziness, visual disturbances, difficulty speaking and episodes of near-fainting whenever she attempted to remain upright. Despite these obvious signs of orthostatic intolerance, doctors diagnosed her with functional neurological disorder (FND) on day 15. A scheduled tilt-table test was cancelled following that diagnosis. Twelve days later, when clinicians finally investigated her cardiovascular response to being upright, they discovered her blood pressure collapsing to 66/52 mmHg. Further testing identified evidence of an immune-mediated autonomic disorder. She subsequently received intravenous immunoglobulin (IVIG) treatment and rehabilitation, improved rapidly and eventually recovered completely.

The case was published in Frontiers in Neuroscience in January 2025 by researchers from Switzerland. Their paper, Case report: Treatable immune-mediated severe orthostatic hypotension in SARS-CoV-2 infection, documents the initial FND misdiagnosis, the physiological abnormalities subsequently discovered and the patient's response to treatment. Importantly, this is not a case in which the patient simply disputed a diagnosis. The researchers themselves acknowledge that FND was diagnosed without documented positive functional signs and that the patient's underlying autonomic dysfunction had initially been missed.

The woman's illness began with a sudden episode in which a black veil appeared over her vision and she became unable to interact, although she did not lose consciousness. She tested positive for SARS-CoV-2, and her initial neurological examination while lying down was unremarkable. Her blood pressure was 132/68 mmHg, with a heart rate of 68 beats per minute. Brain MRI and electrocardiography were normal. However, attempts to assess her cardiovascular response to standing repeatedly failed because she developed severe symptoms, including pallor and difficulty speaking, and had to be laid down to prevent fainting. These were not vague complaints of feeling unwell. The patient was repeatedly demonstrating an inability to tolerate an upright position.

By day four, she required hospitalisation because she could no longer walk and could only occasionally sit upright. Her condition continued to deteriorate, and she was transferred to a specialist neurology department on day 11. Doctors performed extensive investigations, including spinal MRI, lumbar puncture, electroencephalography, electromyography and laboratory testing for autoimmune, inflammatory, infectious and metabolic conditions. None established the cause. Her headaches, psychomotor slowing, cold extremities and impaired balance complicated the examinations, but the persistent inability to tolerate standing remained unexplained. On day 15, clinicians diagnosed FND, and the scheduled tilt-table test was cancelled.

The researchers explicitly acknowledge how the diagnosis was reached:

"The differential diagnosis led to a diagnosis of functional neurologic disorder after ruling out other conditions, rather than being based on the observation of positive functional signs."

In other words, the diagnosis was made because other investigations had failed to identify an explanation, not because clinicians had demonstrated positive signs supporting FND. Yet one of the most relevant investigations had not been completed. The patient could not remain upright without becoming severely symptomatic, and attempts to measure her blood pressure while standing had already failed. Instead of resolving that outstanding question, the FND diagnosis was followed by cancellation of the planned tilt test. The distinction is important: doctors had not demonstrated that her autonomic nervous system was functioning normally. They had simply failed to complete the assessment needed to determine whether it was functioning normally.

The patient entered rehabilitation, but her inability to stand severely restricted her progress. Her symptoms persisted, prompting clinicians to reconsider the diagnosis. On day 27, twelve days after FND had been diagnosed, the team performed a specialised head-up tilt test using an Erigo robotic rehabilitation device. This allowed them to raise the patient progressively while monitoring her blood pressure and heart rate continuously, rather than relying on a conventional standing test she could not tolerate.

The findings were dramatic. Her heart rate initially increased from 85 to 145 beats per minute as her body attempted to compensate for the upright position. After several minutes, that response became insufficient to maintain adequate circulation. Her blood pressure fell progressively, her heart rate began dropping, and she developed pallor, vertigo, difficulty speaking, fluctuating alertness and head drooping. The test had to be stopped after five minutes when her blood pressure reached 66/52 mmHg. Clinicians had finally recorded the physiological abnormality underlying the symptoms that had prevented her from standing since the beginning of her illness.

The sequence of events makes the diagnostic failure particularly clear:

  • Day 1: The patient presented with severe orthostatic symptoms, including visual disturbances and near-fainting. She tested positive for SARS-CoV-2.
  • Day 4: Hospitalised because she could no longer walk and could barely sit upright.
  • Day 11: Transferred to a specialist neurology department for further investigation.
  • Day 15: Diagnosed with FND despite no documented positive functional signs. Her scheduled tilt-table test was cancelled.
  • Day 27: Specialised testing finally revealed severe orthostatic hypotension, with blood pressure collapsing to 66/52 mmHg.
  • Day 28: Began five days of intravenous immunoglobulin (IVIG) treatment for suspected immune-mediated autonomic dysfunction.
  • Day 42: Repeat testing demonstrated a normal cardiovascular response following treatment and rehabilitation.
  • Three months after discharge: Further testing identified a 27% reduction in cerebral blood flow when upright, despite a normal blood-pressure response.
  • 15-month follow-up: The patient had recovered completely and returned to work.

The diagnosis was severe orthostatic hypotension associated with autonomic dysfunction. Orthostatic hypotension occurs when blood pressure drops abnormally upon assuming an upright position, potentially reducing blood flow to the brain and causing dizziness, weakness, visual disturbances and fainting. In this patient's case, the cardiovascular response was sufficiently abnormal to explain her profound intolerance of sitting and standing. The findings also demonstrated why a normal neurological examination conducted while lying down, together with normal conventional imaging, had not excluded a serious physiological disorder.

Further investigation suggested an immune-mediated cause associated with her SARS-CoV-2 infection. Serum collected before treatment was subsequently found to contain eight autoantibodies, including antibodies targeting adrenergic and muscarinic receptors involved in autonomic nervous system regulation, along with components of the renin-angiotensin-aldosterone system responsible for blood-pressure regulation. The researchers considered these findings consistent with an immune-mediated process affecting cardiovascular autonomic control. They also acknowledged that the precise biological effects of the individual antibodies had not been demonstrated, meaning their direct pathogenic roles remained uncertain.

On day 28, the patient began a five-day course of IVIG at 0.4 g/kg per day, alongside intensive rehabilitation. Her improvement was rapid. By day 42, repeat upright testing demonstrated a normal cardiovascular response, and she was discharged able to stand, walk and jump without dizziness. Three months later, she experienced some fatigue, concentration difficulties and mild orthostatic symptoms. Although her blood pressure response remained normal, Doppler ultrasound revealed a 27% reduction in cerebral blood flow when upright, providing further evidence of a physiological abnormality despite the absence of significant orthostatic hypotension at that stage. After additional outpatient rehabilitation, she made a complete recovery and returned to work by the 15-month follow-up.

The researchers were unusually candid about the consequences of the initial diagnostic approach. They noted that patients who are difficult to assess can receive suboptimal care when clinical history and examination are incomplete, leading to unnecessary investigations, diagnostic delays and misdiagnosis. They also acknowledged that unfamiliar manifestations of emerging diseases, including immune-mediated autonomic complications of COVID-19, can contribute to these failures.

"Without this interdisciplinary approach in the very acute phase, these symptoms would have been considered 'functional.'"

That statement is particularly revealing. The authors recognised that without the additional testing, this woman's symptoms could have continued to be classified as functional. Nothing about the patient's presentation suddenly changed to make the disorder physiological. The abnormality had been present while she was being investigated, while she was diagnosed with FND and while she struggled through rehabilitation. What changed was that clinicians finally used a method capable of measuring it.

The most troubling part of this case is not simply that an initial diagnosis proved incorrect. Medical diagnoses can change as new evidence emerges, particularly when a disease is uncommon or difficult to investigate. The problem is that a test specifically relevant to the patient's principal symptoms was cancelled after an FND diagnosis had been established. She had repeatedly demonstrated severe orthostatic intolerance, yet her inability to complete ordinary standing assessments did not lead to successful alternative testing until nearly four weeks after symptom onset. The subsequent results showed precisely why that investigation mattered.

Nor was this a case where doctors had exhausted every meaningful physiological possibility. They had performed numerous investigations, but the quantity of tests is not the same as the completeness of an investigation. A normal MRI cannot rule out autonomic dysfunction. A normal EEG cannot establish that blood pressure is adequately regulated when standing. And a neurological examination conducted while a patient is lying down cannot establish what happens to cerebral circulation when that patient attempts to stand. The eventual diagnosis depended on examining the physiological system most directly implicated by her symptoms.

The case also exposes the danger of treating an FND diagnosis as an endpoint rather than remaining willing to investigate unresolved findings. Once the diagnosis was established, the scheduled tilt test was cancelled, even though the patient's most disabling symptom had not been explained. Only after her continued deterioration and failure to tolerate rehabilitation did clinicians return to the question of orthostatic dysfunction. By then, the investigation had already been delayed for twelve days following the FND diagnosis.

This single case cannot tell us how frequently similar diagnostic failures occur, and it does not establish that every patient diagnosed with FND has an undetected autonomic or immune-mediated disorder. It does, however, document a specific diagnostic failure: a patient with severe orthostatic symptoms received an FND diagnosis without documented positive functional signs, an appropriate investigation was cancelled, and subsequent objective testing identified a serious physiological abnormality. The patient ultimately received treatment and recovered, but only after clinicians revisited what had been left unexplained.

The lesson is not complicated. When a patient cannot stand without becoming severely ill, the inability to stand needs to be investigated. Normal results from unrelated tests do not make an unexplained symptom functional. And when an FND diagnosis results in cancellation of a clinically relevant investigation, the diagnosis risks becoming an obstacle to discovering what is actually wrong. In this case, the difference between being considered functionally disabled and receiving treatment for severe autonomic dysfunction was a test that should never have been abandoned.

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