Neurogenic stunned myocardium in Guillain–Barré syndrome

Case report.

A previously healthy 29-year-old woman who was 7 weeks’ postpartum presented with a 1-week history of cramping in the feet followed by mild, symmetric arm and leg weakness, dysphagia, and dysarthria. There were no antecedent illnesses. On initial examination, her heart rate was 80, her blood pressure was 130/80, and she was afebrile. There was no bulbar or respiratory weakness. She had distal four of five weakness of both hands and of the proximal and distal leg muscles. There was diminished vibratory sensation at the toes bilaterally. Deep tendon reflexes could not be elicited, and the plantar reflexes were flexor. The CSF had an elevated protein (68 mg/dL) and was acellular. Nerve conduction studies showed prolonged distal latencies, slow conduction velocities, and evidence of conduction block; needle electromyogram showed scattered fibrillations and decreased recruitment.

The clinical diagnosis was GBS. She was treated with 2 g/kg of IV immunoglobulin over 5 days, followed by 18 L of plasma exchange over 5 days. During this period, her weakness progressed to flaccid quadraparesis with respiratory compromise, and she was electively intubated on the 5th hospital day, corresponding to the 12th day of her illness. By the 15th hospital day, she was extubated and her limb strength had improved. However, on the 19th hospital day, further respiratory compromise developed and she was reintubated. Repeat CSF examination showed a protein of 76 mg/dL and 1 white blood cell/μL. Repeat nerve conduction studies showed prolonged motor distal latencies, increased temporal dispersion, absent F waves, absent sensory responses, and acute denervation in the legs, consistent with a demyelinating motor sensory neuropathy with secondary axonal loss. A repeat course of plasmapheresis corresponded with improved strength, although her legs remained severely weak. Results from a motor and sensory nerve biopsy showed myelin breakdown, consistent with GBS. Etiologic investigations, including HIV, Epstein–Barr virus, varicella zoster virus, herpes simplex virus type-1 and type-2, cytomegalovirus, anti-extractable nuclear antigen, anti-DNA, anti-sulfatide, anti-GM1, anti-MAG, anti-Gd1b, anti-Gq1b, and anti-HU titers were all normal or negative, as were test results of CSF cytology, CSF Lyme titer, thyroid function, angiotensin-converting enzyme level, serum quantitative immunoglobulin, c-ANCA, urine heavy metal and porphobilinogen levels, and cryoglobulins. Antinuclear antibody was positive to 1:40 with a speckled pattern, and the antihepatitis-B core antibody was positive, although liver enzymes were normal.

Before her neurologic illness, she had no known cardiac disease or symptoms and no risk factors for heart disease. Her ECG on admission was normal, with a rate of 70 and no evidence of ischemia. However, on the third hospital day, when her neurologic status acutely worsened, sinus tachycardia developed to a maximum of 120 beats per minute. An ECG showed diffuse, symmetric T-wave inversions in leads I, II, avL, and V1-V6 and a QTc of 0.473 second (figure). A transesophageal echocardiogram performed the following day showed apical akinesis and diffuse LV hypokinesis with a severely reduced ejection fraction (25%). There was no associated hypotension. On the same day, serum creatine kinase was 245 U/L (normal, 39–238) with 2.7% segregating as CK-MB (normal, <2.0%), serum epinephrine was 880 pg/mL (normal, 110–410), and a 24-hour Holter monitor showed severely reduced heart rate variability with a mean cardiac cycle length of 530 ± 32 msec (normal, 141 ± 39 msec). Twenty-four-hour power spectral analysis showed severely reduced high-frequency power (20.5 msec²; normal, 975 ± 203 msec²) consistent with parasympathetic withdrawal, and the ratio of low-frequency to high-frequency power was consistent with a shift in sympathovagal balance toward sympathetic predominance (3.75; normal, 1.5–2).8 By hospital day 9, the T-wave inversions had resolved, although she remained tachycardiac. A repeat echocardiogram on hospital day 24 showed a normal ejection fraction with no regional or global wall motion abnormalities. There were no further cardiac complications.

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Figure. Twelve-lead electrocardiogram performed on the 3rd hospital day and 10th day of illness showing diffuse symmetric T-wave inversion in leads I, II, aVL, and V1–V6 and severe QTc prolongation (0.473 second).

Discussion.

We describe for the first time a case of acute neuropathy complicated by reversible LV dysfunction, which was presumably neurogenic in origin. Our patient, a healthy young woman, had no history or signs of cardiac dysfunction on her initial presentation. Early in the course of what proved to be a severe demyelinating polyneuropathy requiring mechanical ventilation, a diffuse, symmetric T-wave inversion and QTc prolongation developed, ECG changes that have been correlated with LV dysfunction after SAH.1 There was mild elevation of serum CK-MB and echocardiographic evidence of both segmental and global LV hypokinesis. Follow-up ECG and echocardiography 3 weeks later showed that the entire syndrome had resolved. The rapid onset and resolution of the syndrome, the characteristic ECG and echocardiographic changes, the association of the syndrome with an acute, severe neurologic illness, and the absence of other identifiable cardiac risk factors in an otherwise healthy young woman fulfill the criteria for NSM.1,3

One potential problem with our interpretation of the clinical data is that the patient was 7 weeks’ postpartum and had no baseline echocardiogram before the onset of her acute neuropathy. Therefore, one could argue that the wall motion abnormalities documented on her first echocardiogram might have predated the onset of her neurologic illness. However, she had no history of cardiac disease during or immediately after her pregnancy, and her ECG only began to show abnormalities as her neuropathy worsened. The CK-MB levels were only minimally elevated (which is typical of NSM),1,2 and the syndrome resolved completely over time, which would not be expected if she had peripartum cardiomyopathy. Although we did not perform coronary angiography, we had no reason to suspect coronary artery disease in a young woman with no risk factors. Severe inflammatory myocarditis has been described in GBS9 but is extremely rare and would be unlikely to improve over a period of weeks. Because a myocardial biopsy was not performed, the cause of the cardiac disturbance in our patient remains speculative; however, we believe the preponderance of evidence supports the diagnosis of NSM.

This report expands the range of illnesses that may produce NSM to include diseases of the peripheral nervous system and contributes to our understanding of the pathogenesis of neurogenic cardiac injury. Contraction band necrosis resulting from increased sympathetic tone and catecholamine toxicity is thought to be the pathologic substrate of NSM.1,3 In fact, microneurographic studies have documented sympathetic hyperactivity in GBS,10 which may reflect impaired baroreceptor modulation. Our patient showed a severe reduction in heart rate variability and a shift toward a predominantly low-frequency autonomic modulation of heart rate, consistent with increased sympathetic tone, a vagolytic effect, or both. Studies of circulating catecholamines in SAH have failed to show increased levels in patients with ECG changes, implicating direct neural stimulation, rather than systemic adrenergic secretion, in the pathogenesis of neurogenic cardiac injury.1 Our patient had an elevated serum norepinephrine level when echocardiographic abnormalities developed. Whether elevated circulating catecholamine levels, increased sympathetic outflow via the cardiac nerves, or both caused her LV dysfunction cannot be determined from this single clinical observation.

The possibility that NSM may occur in GBS has clinical implications for the treatment of patients with dysautonomia from acute peripheral neuropathies. Dysautonomia is common in GBS, often causing profound swings in blood pressure or sustained hypotension.6 Although this has been ascribed to dysregulation of venomotor tone or systemic vascular resistance,6 impaired LV performance, as documented in this case, might also contribute to hypotension in GBS and should be looked for in patients with ECG changes and cardiac enzyme elevations. In our patient, the degree of cardiac dysfunction was not severe enough to cause hypotension. However, in more severely affected, older, or volume-depleted patients, a similar degree of cardiac dysfunction could lead to hemodynamic instability, as it sometimes does in SAH.1,2 Echocardiography should be performed in patients with GBS with labile blood pressure, abnormal ECG findings, or cardiac enzyme elevations, and hemodynamic monitoring and vasopressors should be instituted as needed to prevent systemic sequelae of hypotension.

NSM may occur in patients with GBS. We hope that this report stimulates more systematic investigation of cardiac dysfunction in acute peripheral neuropathies, allowing a determination of the generalizability of this clinical problem and a fuller understanding of its pathogenesis.