Hypertension, hyperekplexia, and pyramidal paresis due to vascular compression of the medulla

patients with systemic and neurologic disease.7,10 To show the unique presence of aPE in the CSF of this patient, we tested CSF from two children without HSP to determine whether aPE is a CSF constituent. Additionally, we tested the serum of two adults with active HSP associated with renal but not neurologic complications; neither had aPE. Thus, we conclude that aPE by itself is not necessarily associated with HSP. Our patient may represent a new variant of antiphospholipid antibody syndrome. Antiphosphatidylethanolamine antibody in CSF and blood may be an important marker for patients with putative HSP who have strokes. If additional children with fever, rash, focal neurologic deficits, and renal involvement are positive for aPE in blood and CSF, we plan to study these antibodies by using immunohistochemical means to identify their tissue reactivity and investigate their pathogenic potential.

Acknowledgment The authors thank Drs. LeRoy H. King, Jr. and William H. Dick for HSP patient blood samples and Dr. Antoinette F. Hood for dermatopathologic diagnosis.

Hypertension, hyperekplexia, and pyramidal paresis due to vascular compression of the medulla

References 1. Gibson LE, Su WP. Cutaneous vasculitis. Rheum Dis Clin North Am 1995;21:1097–1113. 2. Lewis IC, Philpott MG. Neurologic complications in the Schonlein-Henoch syndrome. Arch Dis Child 1956;31:369 –371. 3. Ostergaard JR, Storm K. Neurologic manifestations of Schonlein-Henoch purpura. Acta Paediatr Scand 1991;80: 339 –342. 4. Berard M, Chantome R, Marcelli A, Boffa MC. Antiphosphatidylethanolamine antibodies as the only antiphospholipid antibodies. J Rheumatol 1996;23:1369 –1374. 5. Wagenknecht DR, Fastenau DR, Torry RJ, Carter CB, Haag BW, McIntyre JA. Antiphospholipid antibodies (aPL) are a risk factor for early renal allograft failure: isolation of aPL from a thrombosed renal allograft. Transplant Proc 1999;31: 285–288. 6. Gargiulo P, Goldberg J, Romani B, et al. Qualitative and quantitative studies of autoantibodies to phospholipids in diabetes mellitus. Clin Exp Immunol 1999;118:30 –34. 7. Martinez-Cordero E, Rivera Garcia BE, Aguilar Leon DE. Anticardiolipin antibodies in serum and cerebrospinal fluid from patients with systemic lupus erythematosus. J Investig Allergol Clin Immunol 1997;7:596 – 601. 8. Wagenknecht DR, Sugi T, McIntyre JA. The evolution, evaluation and interpretation of antiphospholipid antibody assays. Clinical Immunology Newsletter 1995;15:28 –38. 9. Sornas R, Ostlund H, Muller R. Cerebrospinal fluid cytology after stroke. Arch Neurol 1972;26:489 –501. 10. Gallo P, Sivieri S, Ferranrini AM, et. al. Cerebrovascular and neurological disorders associated with antiphospholipid antibodies in CSF and serum. J Neurol Sci 1994;122:97–101.

Article abstract—MRI showed impingement of the vertebral artery on the left lateral medulla in two patients with arterial hypertension, exaggerated startle reflexes (hyperekplexia), and progressive spastic paresis. One patient underwent microvascular decompression with normalization of arterial hypertension, disappearance of hyperekplexia, and improvement of spastic paresis. The combination of arterial hypertension, hyperekplexia, and progressive spastic paresis should arouse suspicion of neurovascular compression of the lateral medulla. NEUROLOGY 2000;55:1381–1384

F. Salvi, MD, PhD; M. Mascalchi, MD, PhD; C. Bortolotti, MD; S. Meletti, MD; R. Plasmati, MD; G. Rubboli, MD; S. Stecchi, MD; N. Villari, MD; F. Calbucci, MD; and C.A. Tassinari, MD

Neurogenic arterial hypertension secondary to pulsatile vascular compression of the lateral medulla may be cured by microvascular decompression (MVD).1,2 We report two patients with combined arterial hypertension, hyperekplexia (i.e., exaggeration of the

From the Divisione di Neurologia (Drs. Salvi, Meletti, Plasmati, Rubboli, and Tassinari), Dipartimento di Neuroscienze, Universita` di Bologna, Ospedale Bellaria; the Divisione di Neurochirurgia (Drs. Bortolotti and Calbucci), Dipartimento di Neuroscienze, Ospedale Bellaria, Bologna; the Centro Sclerosi Multipla (Dr. Stecchi), Azienda USL Citta` di Bologna; and Sezione di Radiodiagnostica (Drs. Mascalchi and Villari), Dipartimento di Fisiopatologia Clinica, Universita` di Firenze, Florence, Italy. Presented at the 51st annual meeting of the American Academy of Neurology; Toronto, Ontario, Canada; April 17–24, 1999. Received February 7, 2000. Accepted in final form June 23, 2000. Address correspondence and reprint requests to Dr. Mario Mascalchi, Sezione di Radiodiagnostica, Dipartimento di Fisiopatologia Clinica, Universita` di Firenze, Viale Morgagni 85, 50134 Florence, Italy.

startle reflexes [SR]),3 and progressive pyramidal syndrome with vascular compression of the left lateral medulla. MVD was performed in one patient, reversing all findings. Case reports. Patient 1. A 54-year-old woman was admitted to the hospital with progressive gait disturbance. Since age 37 she had complained of sudden involuntary jerks characterized by brisk flexion of the upper and lower limbs. These were initially caused by unexpected noises, but later occurred spontaneously. At age 42, she noted weakness of the right foot, which in few months extended to the whole leg. At age 50, mild dysarthria, dysphagia, and urinary urgency appeared and weakness extended to the left leg, making it impossible for her to walk without support. At age 52 she had several episodes of headache, sweating, and facial flushing associated with arterial blood pressure as high as 210/120 mm Hg with an average restCopyright © 2000 by AAN Enterprises, Inc.

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Figure 1. Patient 1. (A) Axial T1weighted (repetition time [TR], 33 msec; echo time [TE], 13 msec; flip angle 45°) gradient echo MRI at the level of the upper medulla demonstrates contact of the left vertebral artery and left lateral medulla (white arrow) and low signal of the left bulbar pyramid and left lateral medulla (black arrow). (B) Axial proton-density–weighted (TR, 1800 msec; TE, 50 msec) spin echo MRI at the level of the upper medulla shows high signal of the left lateral medulla extending to the midline.

Figure 2. Patient 1. Two polygraphic extracts of audiogenic (A) and spontaneous jerks (C). In (B) and (D), the rectified electromyographic (EMG) averages of five jerks are reported. The same pattern of muscular recruitment is present in audiogenic and spontaneous jerks except for an initial EMG burst on the orbicularis oculi (ORB.OC.) (asterisk) in the audiogenic jerks. Sternocleidomastoideus (SCM) contraction is followed by progressive activation of other muscles innervated by cranial and spinal nerves. In all muscles, each jerk is characterized by an initial EMG burst lasting 300 to 1000 msec, followed by a contraction sustained for several seconds, progressively decreasing in amplitude. MASS. ⫽ masseter; DELT. ⫽ deltoid; A.P.B. ⫽ abductor pollicis brevis; RE.FEM. ⫽ rectus femoralis; TIB.ANT. ⫽ tibialis anterior; L ⫽ left.

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Figure 3. Patient 2. Axial T2-weighted (repetition time, 2000 msec; echo time, 100 msec) spin echo MR image at the level of the lower medulla shows impingement of the left vertebral artery on the left lateral medulla and a circumscribed area of signal change (arrow) in the underlying parenchyma.

ing blood pressure of 180/120 mm Hg; she began taking an angiotensin-converting enzyme inhibitor (delapril), 15 mg/d orally. Neurologic examination at admission showed dysarthria, deviation of the soft palate to the right side, and spastic tetraparesis with bilateral Babinski’s signs. No sensory deficit was present. Blood pressure was 165/100 mm Hg. Jerks occurred spontaneously in the recumbent position and were consistently elicited by sudden, unexpected noise and glabella, or hand tapping. Blood analysis including search for anti-DNA, antinuclear antibodies (anti-ANA), and extractable nuclear antigen (anti-ENA) antibodies were negative. CSF examination, including cell count and IgG index, was normal. There were no oligoclonal bands. Cranial MRI (figure 1) and MR angiography revealed tortuosity of the distal tract of the left vertebral artery that mildly impinged on the left lateral medulla and an area of signal change of the underlying brain parenchyma that extended to the pyramids. The patient underwent split-screen video polygraphy. Several spontaneous and audiogenic jerks were recorded (figure 2). No habituation to the auditory stimuli was observed. The jerks consisted of a stereotyped generalized flexion reaction characterized by grimacing, flexion of the neck, trunk and lower limbs, and associated with abduction of the flexed upper limbs. Jerks were not associated with EEG changes. Following transcranial magnetic stimulation, no motor evoked potential (MEP) was recorded in the tibialis anterior muscles. Amplitudes of rest and activated MEP in the upper limbs were decreased and central motor conduction time was 10.8 (normal, ⬎8.0 ) msec in right abductor pollicis brevis and 8.4 msec in the left abductor pollicis brevis. Somatosensory evoked potentials, blink reflex, and brainstem auditory evoked responses were normal. The patient underwent left retromastoid craniotomy, which confirmed compression on the left lateral medulla;

MVD was performed. After surgery a remarkable decrease of spontaneous and audiogenic jerks was observed. Ten months later, the jerks had disappeared, blood pressure was 140/90 mm Hg with antihypertensive therapy, and the patient could walk with bilateral support. Lower limb strength was increased and spasticity was decreased. The right deviation of the soft palate was unchanged. Transcranial magnetic stimulation showed lack of MEP in the lower limbs, whereas upper limb MEP amplitudes were slightly increased compared with pretreatment values. MRI showed disappearance of the vascular impingement with persistent signal changes in the left lateral medulla and bulbar pyramids. Patient 2. A 74-year-old woman presented with progressive gait disturbance. She had a 10-year history of arterial hypertension. Neurologic examination showed right pyramidal syndrome and mild loss of vibration sense in the right leg. Cranial MRI (figure 3) revealed impingement on the left lateral medulla by the left vertebral artery and a small area of signal change in the underlying parenchyma without other focal brain lesions. One year later, neurologic examination showed a moderate right hemiparesis and a mild left pyramidal syndrome. In addition, she suffered auditory-induced hyperekplexia for 4 months. Split-screen video polygraphy showed that the jerks had the same activation pattern as seen in Patient 1. Transcranial magnetic stimulation showed decreased amplitude of rest and activated MEP on the right anterior tibialis muscle and asymmetrical central motor conduction time (15.9 msec on the right and 14.8 msec on the left; normal, ⬎16). MEP were normal in the upper limbs. She refused MVD surgery.

Discussion. Neurogenic arterial hypertension is usually associated with arterial dolichoectasia (i.e. enlargement, tortuosity, or elongation4 of the intracranial vertebral artery). The normalization of blood pressure observed after MVD points to a functional rather than structural derangement as the pathophysiologic basis of neurogenic hypertension. Two mechanisms are hypothesized: compression of the lateral medulla causing ischemia and excitation of a small group of neurons (C1 area) in the reticular nucleus of the rostroventrolateral medulla that are the main regulators of arterial blood pressure via the reticulospinal sympathoexcitatory vasomotor pathway5; and hyperstimulation of C1 cell group caused by compression of the root-entry zone of the IX and X cranial nerves that contain afferent fibers from myocardial receptors.6 Hyperekplexia may be inherited,7 occurs in several diseases involving the brainstem,3,8 and has been reported to be associated with neurovascular compression.9 The disappearance of hyperekplexia after MVD in Patient 1 strongly supports a causal relationship between the former and neurovascular compression and suggests that hyperekplexia might reflect a functional alteration. The SR is a physiologic response characterized by a widespread muscle contraction that follows sudden, unexpected (usually auditory) stimuli.8 The SR generators, located in the brainstem, receive input from the ventral nucleus November (1 of 2) 2000

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of the lateral lemniscus and project to cranial and spinal nerve motor neurons, probably via the pontomedullaryreticularformationratherthanthecorticospinal pathways. We propose that neurovascular compression of the lateral medulla may cause hyperekplexia through reduction of inhibitory control of the SR center. Corticospinal tract damage secondary to vascular compression of bulbar pyramids is uncommon. 4,10 In Patient 1, it was associated with MRI signal changes and incomplete clinical recovery after MVD. These two aspects suggest a structural, rather than purely functional, derangement. Although we cannot establish the pathophysiologic basis of the signal changes, their persistence after MVD indicates that they could reflect regional ischemia in the territory of the perforating branches arising from the vertebral arteries, possibly due to slow flow or compression, kinking, and torsion of the dolichoectatic artery 4, in addition to the effects of the vascular compression on the brainstem. References

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severe refractory neurogenic hypertension. Neurosurgery 1998;43:1–9. Akimura T, Furutani Y, Jimi Y, et al. Essential hypertension and neurovascular compression at the ventrolateral medulla oblongata: MR evaluation. AJNR Am J Neuroradiol 1995;16: 401– 405. Brown P, Rothwell JC, Thompson PD, Britton T, Day B, Mardsen CD. The hyperekplexia and their relationship to the normal startle reflex. Brain 1991;114:1903–1928. Ince B, Petty GW, Brown RD, Chu CP, Sicks JD, Whisnant JP. Dolichoectasia of intracranial arteries in patients with first ischemic stroke. Neurology 1998;50:1694 –1698. Reis DJ, Golanov EV, Ruggiero DA, Sun MK. Sympathoexcitatory neurons of the rostral ventrolateral medulla are oxygen sensors and essential elements in the tonic and reflex control of the systemic and cerebral circulations. J Hypertens 1994;12(suppl 10):S159 –S180. Thoren P. Role of cardiac vagal C-fibers in cardiovascular control. Rev Physiol Biochem Pharmacol 1979;86:1–94. Matsumoto J, Fuhr P, Nigro M, Hallet M. Physiological abnormality in hereditary hyperekplexia. Ann Neurol 1992;32:41– 50. Brown P, Rothwell JC, Thompson PD, Britton T, Day B, Mardsen CD. New observation on the normal auditory startle reflex in man. Brain 1991;114:1891–1902. Gambardella A, Valentino P, Amnesi G, et al. Hyperekplexia in a patient with a brainstem vascular anomaly. Acta Neurol Scand 1999;99:255–259. Hongo K, Nakagawa H, Morota N, Isobe M. Vascular compression of the medulla oblongata by the vertebral artery: report of two cases. Neurosurgery 1999;45:907–910.