Introduction

Benedikt’s syndrome (BS) is a classical and rare midbrain syndrome characterized by a ipsilateral third nerve palsy and contralateral hemiparesis, hemiataxia, and hyperactive tendon reflexes [6]. It is usually due to a cerebrovascular event, more frequently an infarction of a basilar or posterior cerebral artery branch [16]. Benefit of pharmacotherapy for BS is limited [7]. Deep brain stimulation (DBS) has emerged as the primary option for movement disorders. We report the treatment of DBS for a BS, which was caused by the hemorrhage of midbrain and the effectiveness, steadiness, and mechanism are discussed.

Case report

History, physical examination, and imaging

The patient was a 38-year-old man with a history of sudden hemorrhage in the right midbrain 22 years ago. Three months after the vascular accident, the patient developed diplopia, combination of rest, postural and intentional tremor, mild dystonia, and deterioration of fine motor function in the left limbs. He also had left hemiparesis at the beginning, but gradually recovered to normal. Because of the short duration and intolerable side effects of medication, pharmacotherapy for the patient was unsuccessful and above symptoms became worse with time, which greatly affected his living and working quality (Video 1).

Neurological examination revealed a (1) ipsilateral (right) third cranial nerve deficit (Fig. 1): The patient’s globe was in an oblique position, and he had limited elevation, depression, and adduction. Cranial nerve examination demonstrated mydriasis and an 8-mm, round, and non-reactive pupil. On the contralateral (left) side, (2) he presented as rest, postural, and intentional limb tremor; (3)mild dystonia, (4) superficial sense disturbance; and (5) hyperactive tendon reflexes. (6) His finger-nose test, heel-knee-tibia test, and posterior drawer test were positive, which indicated hemiataxia. Myodynamia of the patient was normal and no pathological reflexes were observed.

Fig. 1
figure 1

Right third cranial nerve deficit. The patient’s right globe is in an oblique position (a); mydriasis and an 8-mm, round, and non-reactive pupil on the right (b), while it is normal on the left side (c); he had limited elevation (d), depression (e), and adduction (f) in the right eye, while it is normal of the abduction (g)

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Computed tomography showed right midbrain hemorrhage 22 years ago (Fig. 2). Magnetic resonance imaging (MRI) showed abnormal signal in the right midbrain, which was considered as cavernous hemangioma (Fig. 3). Magnetic resonance angiography showed negative result in vessels.

Fig. 2
figure 2

Computed tomography 22 years ago. Black arrows indicate the hemorrhage in the right midbrain

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Fig. 3
figure 3

Magnetic resonance imaging of the patient. The black arrows show lesions and cavernous hemangioma in the right midbrain in T2-weight

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Evaluation, surgery, and follow-up

The patient scored 3/4 of the Washington Heights Inwood Genetic Study of Essential Tremor (WHIGET) tremor rating scale [13]. Respectively, he scored 29 and 28 in the Mini-Mental State Examination and Montreal Cognitive Assessment, which suggested that there was no intellectual deficiency. He was diagnosed with BS by neurologist in our hospital. Because of the limited benefit from medication, DBS of right thalamic ventral intermediate (VIM) nucleus was scheduled.

The patient underwent DBS implantation in the right VIM 3 years ago (type 3389 electrode and Activa SC implantable pulse stimulator, Medtronic, Minneapolis, MN, USA). The stereotactic frame was fixed and then MRI was scanned. Target coordinate of VIM was calculated using the surgiplan software, which was 13 mm lateral to the anterior commissural–posterior commissural (AC–PC) line, 6 mm anterior to PC, and on the level of AC–PC line. Under local anesthesia, the microelectrode was inserted into the target coordinate and was confirmed using microelectrode recording and macrostimulation. In the meantime, we find obvious alleviation of tremor and satisfactory threshold for side effects. At last, the electrode was connected to the extension wires and the implantable pulse generator was implanted under general anesthesia. After surgery, MRI was scanned (Fig. 4) and fused with the MRI before surgery. The final coordinate was confirmed correctly and listed as follows: 13.5 mm lateral to the AC–PC line, 6.3 mm anterior to PC, and on the level of AC–PC line. At the initial programming (1 month after surgery), stimulation parameters were amplitude 2.6 V, pulse width 120 μs, rate 200 Hz, using case positive, contact 3 negative, and then the patient had satisfactory improvements in tremor and decrease on WHIGET tremor rating scale, which was 1/4. To our surprise, the mild dystonia disappeared, which we considered was caused by the involuntary tremor and interfered the physical examination before surgery, and then after alleviation of the tremor, the mild dystonia disappeared accordingly. Nine months after surgery, stimulation parameters were changed to amplitude 2.9 V, pulse width 120 μs, rate 190 Hz, using case positive, contact 3 negative, which were using until now. In 3 years follow-up, the patient had stable benefit from DBS without extra side effects and scored 1/4 in WHIGET tremor rating scale, which greatly improve his living quality and working efficiency (Video 2).

Fig. 4
figure 4

MRI after surgery. White arrows show the electrode of DBS in T2-Weight

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Discussion

BS is caused by the lesion in different regions of midbrain and specifically manifests a series of symptoms. At the level of the superior colliculi, from ventral to dorsal of midbrain, are the substantia nigra, red nucleus, oculomotor nucleus, and the spinal lemniscus. The third nerve projects from the oculomotor nucleus and travels near the red nucleus. Lesion of the substantia nigra may induce dystonic movement. Lesion of the red nucleus may cause contralateral ataxia and intention tremor. Lesion of the oculomotor nerve accounts for the ipsilateral internal and external opthalmoplegia. Superficial sense disturbance are due to the involvement of spinal lemniscus. Contralateral hemiparesis and hyperreflexia are associated with injury of the cerebral peduncle [16]. Clinically, BS manifests third nerve palsy, hemiataxia, tremor, hemiparesis, dystonia, and hyperactive tendon reflexes [5]. A rubral tremor presents as combination of rest, postural, and kinetic tremor, which is one of the characteristic of BS [4]. Although symptoms of BS vary considerably due to the structures involve with lesions, coincidently, our patient has the classical symptoms of BS.

BS is usually caused by a vascular event (infaction or hemorrhage) in the midbrain, which involves the artery branches of basilar or posterior cerebral artery [1, 2]. Other etiological factors include tuberculosis, tumor, trauma [16], cavernoma [14], surgical complication [3, 6], multilobulated cystic formation [15], infection [11], and metastasis [12]. Etiology of our patient is the hemorrhage of cavernoma in the right midbrain.

Pharmacotherapy for BS sometimes is inapparent and has intolerable side effects [7]. DBS has replaced ablative therapies such as thalamotomy, which are not beneficial uniformly and has high incidence of irreversible surgical complications. So far, DBS has emerged as a non-invasive, reversible, and adjustable treatment, and has become the chief option for movement disorders [8]. Reports of DBS for classical BS are rare. The electrode site and the effectiveness of DBS for BS vary between different centers. Bandt reported successful case management of an intention tremor due to BS through DBS of the lenticular fasciculus with the follow-up of 16 months. The authors also speculated that the lenticular fasciculus could be used as an effective target for the treatment of intention tremor, via its involvement in the modulation of the cerebellar feed forward control of voluntary movements [2]. Fernandez reported that DBS of the globus pallidus significantly improved a patient’s tremor and dystonia associated with BS, which was caused by surgical complication. However, the symptoms of the patient would spontaneously reappear and the benefit only lasted 1–3 h [6]. The rubral tremor is one of the characteristic of BS and reports of VIM DBS for patients with the rubral tremor that can provide good control [4, 18]. Follett reported a successful case of bilateral VIM DBS fort posttraumatic midbrain tremor with a follow-up of 18 months. The authors suggested that activation of posterior subthalamic area/zona incerta and dentatorubrothalamic tract may improve tremors [7]. Peker reported a case of VIM DBS for a rubral tremor due to a thalamic abscess with a follow-up of 30 months, and the patient’s tremor diminished by 90% [17]. Grabska reported a case of a rubral tremor secondary to the infarction of thalamus, and was successfully treated with DBS of the area between ventralis oralis anterior and zona incerta. However, this case only reduced tremor primarily of the upper extremity rather than lower extremity [9]. Our patient has a classical BS, and we propose that our patient who mainly presented as tremor should be considered of VIM DBS, which may regulate and suppress the abnormal activity in the cerebello-thalamo-cortical loop and result in satisfactory alleviation of symptoms [10]. DBS for classic BS in the literature is fairly rare, and the follow-up is normally less than 2 years. We report a successful case of VIM DBS for the treatment of tremor associated with BS with a follow-up of 3 years, who has durable benefit from DBS. Future investigation of control study with large patient cohorts is needed to verify the effectiveness, safety, and steadiness. Limited by case report, our observations cannot conclusively represent the best option for all patients with BS.