Brain-stem compression in vertebrobasilar dolichoectasia. A multimodal electrophysiological study

Clinical Neurophysiology 112 (2001) 1531±1539

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Brain-stem compression in vertebrobasilar dolichoectasia. A multimodal electrophysiological study S. Passero a,*, S. Rossi a, F. Giannini a, D. Nuti b a

Dipartimento di Neuroscienze, Sezione di Neurologia, Universita' di Siena, Viale Bracci, 53100 Siena, Italy b Istituto di Scienze Otorinolaringologiche, Universita' di Siena, Siena, Italy Accepted 17 May 2001

Abstract Objective: To evaluate the effects of mechanical compression of the brain-stem in patients with vertebrobasilar dolichoectasia (VBD). Methods: In the framework of a prospective, observational study that collected clinical and laboratory data in patients with VBD, we studied 20 patients with compression of the brain-stem due to ectatic, tortuous basilar or vertebral arteries. Patients with cerebral lesions other than small lacunae in the white matter of the cerebral hemispheres were excluded from the study. Patients underwent vestibular and auditory function testing, including brain-stem auditory evoked potentials (BAEPs), blink re¯ex (BR), somatosensory evoked potentials (SEPs), and motor evoked potentials (MEPs). Results: Almost all of the patients complained of auditory or vestibular symptoms and none had symptoms or signs of impairment of long tracts or the facial and trigeminal nerves. The most consistent ®ndings were BR abnormalities with prolongation of ipsilateral R1 latency in cases of compression of the pons (10/16) and prolongation of the R2 and R2c latencies with compression of the medulla oblongata (5/15). Subclinical impairment of corticospinal pathways was found in 13 out of 25 instances of compression, and this was more frequent with compression of the pons. Abnormal BAEPs or SEPs were less frequently encountered, and only in cases with compression of the pons. Conclusions: Neurovascular compression of the brain-stem, even with severe distortion, is seldom associated with overt clinical signs, whereas subclinical dysfunctions are relatively frequent. The central pathways of the BR and the corticospinal pathways are more susceptible to compression than acoustic and sensory pathways. BR, MEP and BAEP data provide a functional evaluation of the brain-stem and some cranial nerves, which is lacking in imaging studies. Functional investigations may be useful in the long-term management of these patients, since VBD may be progressive and surgical correction may be required at some stage. q 2001 Elsevier Science Ireland Ltd. All rights reserved. Keywords: Vertebrobasilar dolichoectasia; Evoked potentials; Blink re¯ex; Otoneurology; Brain-stem

1. Introduction Cranial nerve dysfunction (Yu et al., 1982; Resta et al., 1984; Smoker et al., 1986a; Passero and Nuti, 1996) and ischemia in the vertebrobasilar arterial territory (Nishizaki et al., 1986; Echiverri et al., 1989; Milandre et al., 1991; Besson et al., 1995; Passero and Filosomi, 1998) are frequent and well known complications of vertebrobasilar dolichoectasia (VBD). Less often, an elongated basilar artery (BA) may provoke hydrocephalus by compression of the ¯oor of the third ventricle (Breig et al., 1967; Rozario et al., 1978), or ectatic, tortuous basilar or vertebral arteries

* Corresponding author. Tel.: 139-577-585300; fax: 139-577-270260. E-mail address: [email protected] (S. Passero).

may squeeze and displace brain-stem structures (Bollensen et al., 1991). The consequences of mechanical compression and indentation of the surface of the brain-stem are unknown, since this condition has not been systematically investigated and only a few anecdotal reports (Jacobson and Corbett, 1989; Milandre et al., 1993; Kobayashi et al., 1992; Hongo et al., 1993; Himi et al., 1995; Krespi et al., 1995; Hongo et al., 1999) or case series (Milandre et al., 1991) based only on clinical observations are available. The fact that brain-stem compression may be found in asymptomatic patients does not exclude the possibility of it inducing subclinical dysfunction in a speci®c neural system. In this study, 20 patients with brain-stem compression due to VBD were systematically evaluated with otoneurological examination, vestibular function testing and multimodal electrophysiological studies, including sensory (SEPs) and motor evoked potentials (MEPs).

1388-2457/01/$ - see front matter q 2001 Elsevier Science Ireland Ltd. All rights reserved. PII: S 1388-245 7(01)00597-1

CLINPH 2000774

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2. Materials and methods In the framework of a prospective, observational study that collected clinical and laboratory data of patients with VBD, we studied 20 patients who had compression and indentation of the surface of the brain-stem due to ectatic, tortuous basilar or vertebral arteries. Patients with a history of stroke, brain surgery, head trauma or other neurological diseases and patients who had magnetic resonance imaging (MRI) evidence of cerebral lesions, other than small lacunae in the white matter of the cerebral hemispheres, were excluded from the study. Patients were evaluated by a protocol that included the following investigations: vestibular and auditory function testing including brain-stem auditory evoked potentials (BAEPs), blink re¯ex (BR), upper limb SEPs, upper and lower limb MEPs. VBD was diagnosed on the basis of MRI and magnetic resonance angiography (MRA) studies. The MRI study was performed with a 0.5 T magnet using spin-echo, multi-echo and fast techniques. The images were obtained in sagittal, axial and coronal planes. According to Smoker et al. (1986b), the BA was judged to be elongated if, at any point along its course, it lay lateral to the margin of the clivus or dorsum sellae or bifurcated above the plane of the suprasellar cistern. Ectasia was diagnosed if the diameter of the artery was greater than 4.5 mm. Patients were classi®ed according to the anatomical site of compression (pons, medulla oblongata, or both). In 7 patients, the whole neurophysiological protocol was followed-up 1±2 years later. 2.1. Otoneurological investigations Examination of vestibular function was carried out using Frenzel glasses for spontaneous-positional and positioning nystagmus and then by DC electrooculography for gaze, saccades, smooth pursuit and caloric tests. Dynamic imbalance of the vestibular system was also assessed by head shaking and head thrust tests (Halmagyi and Curthoys, 1988). Any nystagmus present in the primary position of the eyes under Frenzel glasses was regarded as pathological (Cohen, 1984). Peripheral or central origin was determined according to Leigh and Zee (1991). Eye movement recordings were performed with an automated electronystagmography package (Siter±Racia, Bordeaux). Gaze-evoked nystagmus was induced by having the patient ®xate on a target (small red light-emitting diodes) 308 to the right, left, above and below the center position. Any nystagmus present under these conditions was regarded as pathological (Baloh and Furman, 1989). Rebound nystagmus was also evaluated by returning the eyes to the primary position. Saccadic movements were induced by random step changes in target position (small red light-emitting diodes). The resting time of the stimulus at each position was randomly varied in the range of 1±2.5 s. The parameters were: accuracy and velocity of ^10 and ^308 for horizontal saccades and ^108 for vertical saccades. Five saccades for

each direction were evaluated. The saccade accuracy was de®ned as the saccade amplitude/target amplitude £ 100. Dysmetria was diagnosed if the saccade accuracy was less than 85% or more than 100% (Pyykko and Schalen, 1984). Horizontal smooth pursuit movements were induced by sinusoidally moving the target ^208 from the mid-position at a frequency of 0.2 Hz. The normal range of gain (target velocity/eye velocity) was .0.6 (Pyykko and Schalen, 1984). Bithermal (30 and 448C) caloric testing was performed according to the Fitzgerald and Hallpike (1942) technique. The slow phase velocity (SPV) and frequency of nystagmus were evaluated. On the basis of our normative data, a caloric asymmetry of greater than 25% was considered abnormal (vestibular paresis or unilateral hypofunction). In patients without response, iced water was used. Bilateral paresis was diagnosed when the SPV was less than 58/s for all responses (Baloh and Furman, 1989). Auditory function was evaluated by pure tone audiometry and BAEPs. Pure tone thresholds were measured by air and bone conduction. BAEPs were performed with a 4 channel Phasis apparatus (Esa-Ote Biomedica, Florence). The patients were tested while lying on a bed inside an echofree room. Surface Ag/AgCl electrodes were placed on the brow (ground), mastoid (exploring electrode) and vertex (reference electrode). The interelectrode resistance was balanced and maintained at less than 5 kV. Single sine wave clicks of 100 ms durations and a frequency of 21 clicks/s were delivered through earphones. The stimulation was repeated 2000 times. The analysis time was 12 ms. The criteria for abnormal BAEPs were: I±III interpeak latency, .2.5 ms; I±V interpeak latency, .4.5 ms; III±V interpeak latency, .2.3 ms. 2.2. Neurophysiological examination SEPs were obtained by electrical stimulation of the left and right median nerves of the wrist with square wave pulses (duration, 200 ms; repetition rate, 1 Hz) eliciting painless thumb opposition. Recordings were performed with a 4 channel Phasis electromyograph (Esa-Ote Biomedica, Florence), with a bandpass ®lter from 10 to 2000 Hz. Recording electrodes were placed over the ipsilateral Erb point referenced to the contralateral Erb point (wave N9), over the spinous process of C7 referenced to an anterior neck electrode (wave N13), and on the scalp area corresponding to the primary sensory cortex, i.e. C3 or C4 of the 10±20 International EEG System, referenced to an ipsilateral auricular electrode (waves P14 and N20). At least two sets of 250 artifact-free responses were averaged for each stimulated side to show the reproducibility of the measured peaks. For the purpose of the present study, the interpeak latencies, N13±N20, corresponding to upper cervical/primary sensory cortex time, and P14±N20, corresponding to the lemniscal/primary sensory cortex interval or central conduction time (sCCT), were considered. The

S. Passero et al. / Clinical Neurophysiology 112 (2001) 1531±1539

criteria for abnormal SEPs were: N13±N20, .6.5 ms; P14± N20, .5.5 ms; and interside latency (either N13±N20 or sCCT), .1.5 ms. Transcranial magnetic stimulation was performed using the commercially available Cadwell MES-10 magnetic stimulator connected to a 9 cm round coil centered on the left or right motor cortex. Individually, scalp sites of stimulation were chosen, keeping the coil in the position, from which MEPs of at least 50 mV of amplitude could be elicited in the relaxed contralateral abductor pollicis brevis and tibialis anterior muscles, with the lowest intensity of stimulation, in at least 50% of 6 trials. This intensity (resting threshold) was then increased by 20% and MEPs were recorded while subjects contracted the target muscles to 10% of the maximum voluntary activation. At least 4 reproducible MEPs were obtained from each muscle via a pair of surface electrodes placed in a belly-tendon montage. The motor central conduction time (mCCT) was calculated by the F-wave method (Rossini et al., 1994). This procedure is routinely employed to investigate corticospinal function in a variety of neurological disorders (Rossini and Rossi, 1998). The criteria for abnormal MEPs were: mCCT of .6.5 ms and mCCT interside latency of .1 ms (abductor pollicis brevis); mCCT of .15 ms and mCCT interside latency of .2.3 ms (tibialis anterior). The BR was recorded by stimulating the supraorbital nerve at the supraorbital foramen utilizing square wave pulses with a duration of 200 ms. The stimulus intensity was adjusted in a stepwise fashion until a stable BR was obtained. Stimuli were delivered at intervals of one/s. Re¯ex responses were recorded bilaterally by surface electrodes with the active electrode placed over the lower half of the orbicularis oculi muscle and the reference at lateral edge of the orbit. The ground electrode was ®xed in the middle of the forehead. The band width was 10 Hz±5 kHz, the analysis time was 100 ms. The shortest onset latencies of R1, R2, and R2c were measured from 5 consecutive trials. The criteria for abnormal BR were: R1 latency, .12 ms; R2 latency, .39 ms; R2c latency, .40 ms. BR response abnormalities were classi®ed according to Aramideh et al. (1997) as corresponding to involvement of the: (A), mid-pons; (B1), Vth nerve pontine entrance; (B2), Vth nerve spinal complex; (C), VIIth nerve pontine exit or VIIth nerve nucleus; (D), Vth nerve spinal complex and crossed interneuron ®bers; (E), lateral tegmental ®eld. The criteria for abnormal BAEPs, BR, SEPs and MEPs were those adopted in our laboratory and are based on our normative data-base. 3. Results The clinical characteristics of the patients and results of electrophysiological and otoneurological studies are reported in Tables 1 and 2. The 20 patients, 6 women and 14 men, ranged in age from 40 to 78 years with a mean age

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of 66.4 ^ 9.7 years. Fourteen patients had a history of arterial hypertension, none had diabetes and none were alcohol abusers. 3.1. Clinical ®ndings Nineteen patients complained of auditory or vestibular symptoms (in one patient, this was associated with a mild dif®culty in swallowing) and one had sialorrhea and velar paresis. Among the patients with auditory±vestibular symptoms, 8 had only vestibular symptoms (imbalance, vertigo and oscillopsia), 7 had auditory symptoms (tinnitus and hearing loss) and 4 had combined auditory and vestibular symptoms. 3.2. MRI ®ndings The diameter of BA ranged from 4.7 to 9.2 mm. The most frequent BA deformation was C-shaped, other types were Sand J-shaped. Fifteen patients also had ectasia and elongation of the vertebral artery (VA), the diameter of which ranged from 4.5 to 6.3 mm. Five patients had compression of the ventrolateral or lateral surface of the medulla oblongata due to the VA, 4 patients had compression of the pons due to the BA, 5 patients had compression of the medulla oblongata (VA) and ipsilateral pons (BA), 5 had compression of the medulla oblongata (VA) and contralateral lower or middle pons (BA) and one patient had compression of the lower pons and contralateral middle and upper pons (BA). In some instances, the compression was even associated with severe distortion of neural structures, particularly the medulla oblongata (Fig. 1). 3.3. Otoneurological ®ndings In 3 patients, the otoneurological ®ndings suggested typical peripheral impairment with a reduced or absent vestibular response and unilateral sensorineural hearing loss. In 8 patients, the ®ndings suggesting peripheral impairment were associated with signs of central dysfunction such as abnormalities in visual ocular control (abnormal saccadic eye movements and abnormal smooth pursuit), or were indicative of isolated central dysfunction. Nine patients had normal otoneurological ®ndings or non-signi®cant bilateral hearing loss. BAERs were abnormal in 11 instances of compression. In 5 of these, the abnormalities were consistent with severe hearing loss or peripheral impairment of the auditory pathways. Abnormalities suggesting dysfunction of a central origin were observed in 6 instances of compression of the pons and in one instance of compression of the pons and ipsilateral medulla oblongata. 3.4. Neurophysiological ®ndings Individual values of the neurophysiological parameters are reported in Tables 3 and 4. Abnormal BR was observed

Vertigo HL R tinnitus, imbalance Vertigo HL, bilateral tinnitus, dysphagia Sialorrhea, L velar paresis HL HL, R tinnitus HL, imbalance, oscillopsia

Vertigo HL, bilateral tinnitus L tinnitus, imbalance Imbalance Vertigo, imbalance, oscillopsia

1/M/73 2/M/74 3/M/63 4/F/48 5/M/70 6/M/57 7/F/71 8/F/58 9/M/40

10/M/69 11/F/78 12/M/65 13/M/72 14/F/63

L pons±medulla R pons±medulla R pons±medulla L pons±medulla R pons±medulla

R pons L pons R pons L pons L medulla L medulla L medulla R medulla R medulla

Site of compression NS, abnormal VOC NS R RVR, R SNHL N NS, abnormal VOC N NS NS Bilateral AVR, R total deafness, L SNHL NS NS NS, abnormal HST and VOC NS Bilateral AVR, abnormal VOC

Otoneurological ®ndings

Abnormal III±V N Abnormal I±III, I±V N N

N N R absent N N N N N R absent; L abnormal I±III, I±V

BAEP

N N Abnormal R2, R2C N Abnormal R1

Abnormal R1 Abnormal R1 N Abnormal R1 N N N N N

BR

N N N N N

N N N N N N N N N

SEP

N N N ISD N

N ISD ISD ISD N N ISD N ISD

mCCT (UL)

N N N ISD N

N N N N N ISD N N N

mCCT (LL)

L, left; R, right; HL, hearing loss; N, normal; NS, non-signi®cant hearing loss; AVR, absent vestibular response; RVR, reduced vestibular response; SNHL, sensorineural hearing loss; HST, head shaking test; VOC, visual ocular control; UL, upper limb; LL, lower limb; ISD, abnormal interside difference.

a

Symptoms

Case/sex/age

Table 1 Clinical, otoneurological and neurophysiological ®ndings in 14 patients with VBD and unilateral compression of the brain-stem a

1534 S. Passero et al. / Clinical Neurophysiology 112 (2001) 1531±1539

Vertigo

Imbalance

HL

Vertigo, imbalance

Imbalance, R tinnitus

2/M/70

3/M/78

4/M/70

5/M/76

6/F/68

L medulla R pons L medulla

R medulla L pons R medulla R pons L medulla R pons

R rostral pons L pons

L caudal pons

Site of compression

R RVR

NS, R AVR, abnormal HST and VOC

NS

L RVR, abnormal VOC

NS, R-beating spontaneous Ny, BAPP Ny, abnormal VOC

NS, abnormal VOC, persistent skew deviation

Otoneurological ®ndings

N Abnormal I±III, I±V N

N Abnormal III±V N Abnormal III±V No response N

R1 R2, R2C R2C

R2, R2C R1

Abnormal R2, R2C Abnormal R1 N

Abnormal Abnormal N Abnormal Abnormal Abnormal

Abnormal R1 Abnormal R1

Abnormal R1

Abnormal III±V Abnormal III±V Absent III and V

BR

BAER

Ny, nystagmus; BAPP, bi-directional apogeotropic persistent positional nystagmus. Other abbreviations as in Table 1.

L tinnitus

1/M/69

a

Symptoms

Case/sex/age

Table 2 Clinical, otoneurological and neurophysiological ®ndings in 6 patients with VBD and bilateral compression of the brain-stem a

N N N

N N N N N N

Abnormal P14±N20 N

Abnormal P14±N20

SEP

N N N

N ISD N N N N

ISD ISD

N

mCCT (UL)

N ISD N

N N N ISD N N

N N

ISD

mCCT (LL)

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S. Passero et al. / Clinical Neurophysiology 112 (2001) 1531±1539

Fig. 1. MRI (repetition time (TR), 34 ms; echo time (TE), 6.9 ms) showing compression and distortion of the medulla oblongata due to ectatic, elongated left VA.

in 11 patients (7 unilateral and 4 bilateral; Fig. 2). The most consistent ®nding was an increased ipsilateral R1 latency (type A) which was observed in 9 instances of compression of the pons and one instance of compression of the pons and ipsilateral medulla oblongata. BR abnormalities compatible with involvement of the Vth nerve spinal complex (type B2) were observed in two instances of compression of the medulla oblongata and one instance of compression of the pons and ipsilateral medulla oblongata. In one patient with compression of the left medulla oblongata and right pons, BR abnormalities were compatible with involvement of the Vth nerve spinal complex and crossed interneuron ®bers (type D). No abnormalities corresponding to an involvement of the Vth nerve pontine entrance (type B1), VIIth nerve pontine exit or VIIth nerve nucleus (type C) or lateral tegmental ®eld (type E) were observed. Absolute values of the N13±N20 interpeak latencies of SEPs were within normal limits in all patients and none had differences in the latency between the two sides exceeding normal limits. In one patient with bilateral compression of the pons, sCCT was bilaterally delayed without an interside difference (Table 4). The latency of P14 wave was normal in all patients. MEPs evoked by magnetic stimulation of the motor cortex and recording from contralateral abductor pollicis brevis muscle were abnormal in 9 patients, 8 of whom had compression of the pons and one had compression of the pons and ipsilateral medulla oblongata. When recorded from tibialis anterior muscles, MEPs were abnormal in 5 patients (4 with compression of the pons and one with compression of the pons and ipsilateral medulla oblongata). Abnormal BAEPs and BR were more frequently observed in patients with bilateral compression of the brain-stem than

Table 3 Individual neurophysiological ®ndings in 14 patients with VBD and unilateral compression of the brain-stem a±c Case

1 2 3 4 5 6 7 8 9 10 11 12 13 14 a b c

BR

SEPs

MEPs

R1

R2

R2c

N13±N20

N13±N20 ISD

P14±N20

P14±N20 ISD

mCCT (UL)

mCCT (UL) ISD

mCCT (LL)

mCCT (LL) ISD

12.2 12.1 10.4 12.6 10.8 11.4 11.2 10.4 9.6 9.6 9.6 11.2 10.8 12.8

34.0 33.6 30.0 34.2 38.4 34.4 33.0 34.4 33.6 33.2 32.0 40.3 32.0 36.0

37.6 36.8 32.8 35.7 37.6 34.2 33.4 36.8 34.0 35.4 32.4 41.7 33.6 34.8

6.4 5.8 5.2 5.7 6.1 5.5 6.5 6.1 6.0 5.1 5.6 5.9 4.5 5.8

0.1 1.1 20.4 0.4 20.2 0.1 0.3 0.1 0.0 20.4 20.3 0.4 20.2 0.5

4.7 4.8 4.2 4.5 4.8 4.3 5.3 5.1 5.0 4.6 4.5 4.8 3.4 4.6

0.5 1.1 20.4 0.2 0.1 0.2 0.2 0.1 0.0 0.1 20.4 0.6 0.2 0.3

4.3 6.4 4.1 5.3 4.3 6.0 4.2 4.2 5.6 3.8 4.0 4.2 6.0 3.1

0.1 1.4 1.3 1.3 20.3 0.2 1.1 20.5 1.2 0.5 20.4 0.7 1.3 0.8

14.2 13.8 13.9 14.6 14.9 14.8 10.6 12.6 12.4 15.0 14.6 14.4 14.2 11.5

0.3 0.1 0.7 20.5 0.9 2.7 1.1 20.8 20.9 0.3 0.4 0.3 2.7 0.4

UL, upper limb; LL, lower limb. All values are expressed in ms. Absolute values refer to the compressed side. Interside difference (ISD) was calculated as the value of the uncompressed side minus the value of the compressed side.

S. Passero et al. / Clinical Neurophysiology 112 (2001) 1531±1539

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Table 4 Individual neurophysiological ®ndings in 6 patients with VBD and bilateral compression of the brain-stem a Case

1

Site of compression

L caudal pons R rostral pons L pons R medulla L pons R medulla R pons L medulla R pons L medulla R pons L medulla

2 3 4 5 6 a

BR

SEPs

MEPs

R1

R2

R2c

N13±N20

P14±N20

mCCT (UL)

mCCT (LL)

12.3 12.8 13.0 11.0 12.4 11.0 13.2 11.6 10.6 10.8 12.4 11.2

30.8 30.4 38.2 39.8 36.2 35.2 35.6 41.4 36.8 41.1 36.0 35.2

31.2 34.0 38.0 44.0 36.4 37.6 34.0 45.4 45.1 42.1 35.6 36.0

6.5 6.4 4.6 5.0 5.2 5.1 5.9 5.9 6.5 6.3 5.3 5.4

6.2 5.8 3.6 4.0 4.4 4.1 4.6 4.9 5.0 5.4 4.3 4.6

2.9 4.8 4.5 3.3 3.8 2.6 2.9 3.5 2.1 2.8 1.8 2.1

17.1 12.4 13.7 14.6 14.4 13.5 11.8 8.7 12.5 14.0 11.6 8.9

All values are expressed in ms. R, right; L, left; UL, upper limb; LL, lower limb.

in patients with unilateral compression, whereas abnormal MEPs were more frequent in the latter. When patients were divided according to the site of brainstem compression, it emerged that the highest percentages of subclinical abnormalities of the central motor, central BR and central auditory pathways were found in patients with compression of the pons (Table 5). Follow-up examinations in 7 patients after 1±2 years con®rmed otoneurological and electrophysiological data in all cases. Worsening of the neurophysiological parameters, but not the clinical condition, was observed in 3 patients (increased mCCT in two patients and increased R1 latency in one patient). 4. Discussion On the basis of ®ndings from the literature, the most frequent complication of VBD seems to be the compression of structures adjacent to the basilar and vertebral arteries.

Fig. 2. Exemplar tracing of BR of a patient (number 4 of Table 4) with compression of the right pons and left medulla oblongata. There was delayed R1 response to right supraorbital nerve stimulation and there were delayed R2 and R2c responses to left supraorbital nerve stimulation.

VBD has been associated with compression of almost all cranial nerves, but the nerves that traverse the cerebellopontine angle cistern seem to be the most frequently involved (Yu et al., 1982; Resta et al., 1984; Smoker et al., 1986a; Passero and Nuti, 1996). The brain-stem, particularly the mid-pons and upper medulla oblongata, may also be compressed and this condition may coexist with neurovascular compression of cranial nerves. Little is known about the effects of mechanical compression and indentation of the surface of the brain-stem in patients with VBD: the few anecdotal reports on the topic suggest that compression may be associated with long tract signs such as pyramidal impairment (Bollensen et al., 1991; Milandre et al., 1991, 1993; Kobayashi et al., 1992; Hongo et al., 1993, 1999), or hemisensory disturbances (Hongo et al., 1993, 1999), with downbeat nystagmus (Jacobson and Corbett, 1989; Krespi et al., 1995; Himi et al., 1995), and other signs (Milandre et al., 1991). On some occasions, these conditions have been treated by surgical neurovascular decompression, i.e. mobilization of the offending vessel, its transposition and ®xation to adjacent structures by means of lyophilized dura, Te¯on felt or synthetic vascular graft material (Kobayashi et al., 1992; Himi et al., 1995; Anson et al., 1996; Hongo et al., 1999), or by other surgical procedures such as proximal occlusion (Hongo et al., 1993; Anson et al., 1996) with subsequent improvement or disappearance of the symptoms. The introduction of MRI, which dramatically improved investigation of the relationships between blood vessels and neural structures, revealed that brain-stem compression may sometimes even occur in asymptomatic patients. Why some patients complain of symptoms and others do not is still unclear; however, several factors, such as the rapidity with which compression occurs, its entity, the site of maximum compression, or the rhythmic component of artery pulsation may play a role. Experimental studies have shown that rapid mechanical compression of the brain-stem induces immediate dysfunction, the entity of which is directly proportional to the

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S. Passero et al. / Clinical Neurophysiology 112 (2001) 1531±1539

Table 5 Distribution of abnormal ®ndings according to the site of compression Site of compression

Abnormal BAER a

Pons (n ˆ 11) Medulla oblongata (n ˆ 10) Pons and ipsilateral medulla oblongata (n ˆ 5) All b

5 0 1

a b

6 (23)

Abnormal R1 9 0 1 10 (38)

Abnormal R2 and R2c

Abnormal SEP

0 3 1

2 0 0

4 (15)

2 (8)

Abnormal mCCT 9 3 1 13 (50)

Any abnormality 10 6 4 20 (77)

Only abnormalities of central auditory pathways were considered. Figures in parentheses represent percentage values.

degree of compression (Zappulla et al., 1985). With slowly progressing compression, as presumably occurs in patients with VBD, the brain-stem even seems to functionally tolerate severe distortion, as in some of our patients, without overt clinical manifestations directly connected with the compression of long tracts or speci®c brain-stem circuits. However, as clearly demonstrated in the present study, the absence of clinical symptoms does not exclude the possibility of more subtle (subclinical) impairment of neural structures. Subclinical impairment of speci®c nervous pathways has been demonstrated in a variety of neurological conditions and with different neurophysiological techniques of functional evaluation of the central nervous system, such as BAEPs, SEPs, BR, and recently, MEPs (Di Lazzaro et al., 1999). In the present study, the most frequent subclinical abnormalities were prolongation of BR components and changes of the MEPs; sensory pathway abnormalities were observed only in two instances (delayed P14±N20 sCCT), and abnormalities of the central auditory pathway were found in a minority of patients. This is clearly related to the anatomical location of pathways and their extensions in the brain-stem. Abnormal otoneurological ®ndings suggesting peripheral or central dysfunction of the auditory±vestibular system are often observed in patients with VBD, and there is a particularly high prevalence of abnormal caloric test results (Passero and Nuti, 1996; Nuti et al., 1996) as in the present study. These ®ndings may be due to mechanisms such as compression of the vestibulocochlear nerve and/or brainstem, or impaired blood supply to the vestibular labyrinth (Passero and Nuti, 1996). The results of the present study lead to the following conclusions: (1), neurovascular compression of the brainstem, even with severe distortion of its structures, is seldom the cause of any overt clinical manifestation, whereas subclinical dysfunctions of speci®c nervous systems are relatively frequent; (2), presumably due to their anatomical position, the central pathways of BR and the corticospinal tracts seem more susceptible to compression-induced damage than the sensory and acoustic central pathways; (3), BR, MEPs and BAEPs provide accurate functional evaluation of the brain-stem and some cranial nerves, which are not obtainable by imaging studies. Functional

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