Introduction

Cerebral palsy (CP) is a heterogeneous group of syndromes that vary with regard to the extent of brain damage, etiology, age, and the progression of movement disorders. The most prominent symptoms are dystonia and spasticity. CP constitutes the largest category of acquired dystonia, and the treatment of acquired dystonia in CP is difficult. Pharmacological treatment and surgical therapies such as selective posterior rhizotomy (SPR), intrathecal baclofen infusion, lesional surgery, and deep brain stimulation (DBS) in the internal segment of the globus pallidus (GPi) have consistently shown disappointing results [1, 2, 3, 4]. Due to the lack of a suitable treatment and a good prognosis for CP, other potential treatments need to be explored and developed.

The presence of different etiologies underlies the variable clinical spectrum of CP, but disruption of motor control is almost always reported [5]. Abnormal communication of the cerebellum with the motor cortex, basal ganglia, and/or brainstem can cause involuntary movements such as dystonia, tremor, and spasticity, [6, 7] and cerebellar stimulation can affect the pathological abnormalities of this network [8]. Here, we report the case of a CP patient with severe spasticity and dystonia who did not respond well to SPR and bilateral GPi DBS therapy, but has experienced significant improvements after superior cerebellar peduncle (SCP) DBS.

Case Presentation

A 21-year-old woman with severe fixed dystonia was referred to our hospital for surgical treatment in July 2017. The patient’s medical history showed that she had birth hypoxia. During her first years of life, she presented unwanted movements and dystonic posturing. At the age of 2 years, she had developed generalized dystonia with severe spasticity and was diagnosed with CP. Her symptoms were refractory to medical therapy and SPR.

She has experienced generalized dystonia with severe spasticity and her speech was also affected. These conditions led her to move using a wheelchair. On admission, she presented with uncontrollable facial expressions and movements, and showed increased muscle tone in the face and the extremities (Figure 4a, Video 1). The patient received GPi DBS in our department in July 2017. GPi DBS were located correctly (Figure 1a–c); however, little stimulation effect was observed after surgery. Her clinical symptoms gradually deteriorated regardless of repeatedly programming (Table 1). At a 2-year follow-up visit, she was unable to sit for prolonged periods of time due to severe spasticity in her trunk and extremities.

In July 2019, the patient consulted our hospital again for further treatment. Upon admission, the patient presented with involuntary movements in multiple body parts including eyes, mouth, neck, trunk, and all four extremities (Figure 4b and c, Video 1). During examination, muscle spasms were found in all four extremities, especially in the left arm, right leg, flexion of the left elbow, and right knee. Due to truncal dystonia, the patient was unable to stand and needed a back support while sitting. In addition, the patient’s speech was laborious, non-fluent, and incomprehensible (Table 3 and Figure 4f). The patient also experienced pain in the extremities (visual analog scale score = 6; Burke-Fahn-Marsden dystonia rating scale movement sub score [BFMDRS] = 93.5; and the disability sub score = 21). The modified Ashworth scale (MAS) for rating the spasticity was three and four for the right arm and other limbs, respectively. The score for quality of life using the 36-item short form health survey (SF-36) was 123, and moderate depression was revealed by a Beck Depression Inventory score of 14.

Due to limited treatment options and the potential role of the cerebellum in dystonia and spasticity, [9] we proceeded with cerebellar DBS. The ethics committee of the Shanghai Jiaotong University School of Medicine approved this procedure. Written informed consent was obtained from the patient and her parents. The surgical procedure is described in detail in Figures 2, 3 legends and the MRI images for determining the coordinates of the target SCPs and DNs are shown in Figure 2.

Results

Outcomes

At the 3-month follow up visit, the BFMDRS showed an improvement of 28.9% (pre-operation = 93.5, post-operation = 66.5), with considerable improvements in activities using the upper extremities, such as brushing teeth and combing by herself. The patient’s voice quality, speech fluency, and self-esteem improved. Notably, the stimulation parameters were reduced to 1+, 2–, and 2.35 V for the right side and 5+, 6–, and 1.75 V for the left side, with a reduced pulse width of 50 µs and a frequency of 130 Hz. The patient was able to sleep much better during nighttime than before surgery. Hence, we set a daily cycling mode with stimulation from 6:30 am till 23:30 pm. Four months after SCP stimulation, the patient presented in a television show.

At the 6-month follow up, the BFMDRS showed an improvement of 36.4% (pre-operation = 93.5, post-operation = 59.5) with considerable improvements in the upper extremities, axial dystonia, and speech, and a slight improvement in the lower extremity dystonia (Figure 4d–e). The patient’s disability scale score reduced to 14, with improvements primarily in her hand and speech. She was able to write and apply makeup for herself, tasks which were impossible before the surgery. Moreover, the patient was able to send voice messages in WeChat. The MAS scores of the upper limbs (right, left) and lower limbs (right, left) post-operation were 1, 2, 4, and 3, respectively, while at pre-operation they were 3, 4, 4, and 4, respectively (Table 3). Notably, the patient was able to sit without a back support and to stand on both legs (Video 1).

Figure 4 

Pre- and post-images representing the symptoms of the patient. (4A) Photograph recorded before GPi DBS surgery. Pre-(4B) and (4C) and post-operation-(4D) and (4E) (cerebellar DBS) photographs of the patient’s general appearance on standing and sitting. (4F) Vocal spectrum before and after the operation.

The SF-36 scale results showed a significant improvement in her quality of life at both the 3- and 6-month follow up. The vocal analysis indicated a much clearer and more fluent speech after surgery. Five months after surgery, the patient hosted a live show on a Chinese network platform. The stimulation parameters were the same as the 3-month follow up with no significant perioperative or hardware-related complications.

Discussion

The present case report demonstrated the ability of SCP DBS to reduce pain, dystonia, and spasticity, and to improve the quality of life in a patient with CP who did not respond well to GPi DBS. Our results confirmed the beneficial effect of DBS administered via the SCP, which links the DN to cortical and subcortical structures.

Recently, evidence of the connections between the cerebellum and basal ganglia has led to a resurgence of interest in the cerebellum involvement in modulating motor functions. The dentato-rubro-thalamic and cerebello-thalamo-cortical tracts are two well recognized pathways that could account for the movement regulatory mechanism of the cerebellum [10]. The cerebellum is believed to directly modulate the basal ganglia, and abnormal cerebellar output has been reported to cause movement disorders [6, 11]. Therefore, many research groups have started to reconsider the efficacy of cerebellar interventions for several disorders including CP.

Before the widespread use of DBS, chronic cerebellum stimulation had long been used to treat patients with CP, the majority of whom showed improvements in dystonia and spasticity. Cooper et al. first treated patients with CP using cerebellum stimulation of the anterior lobe (which contains the SCP) in 1973 [12]. Rose Davis et al. [9] and Galanda et al. [13, 14, 15] have reported that cerebellar anterior lobe stimulation reduced the severity of spasticity in patients with CP.

DBS is conducted by a cylinder lead that can be precisely inserted into deep brain targets such as the DN and SCP using a stereotactic technique. Recently, case reports have demonstrated the efficacy of DN or SCP DBS in patients with dystonia [16, 17, 18]. However, there is limited clinical evidence for the efficacy of cerebellar DBS, and consensus on the selection of appropriate stimulation targets for patients with CP has yet to be reached. In this case, we targeted both SCP and DN with a single DBS, and both targets alleviated the patient’s symptoms. Unfortunately, DN stimulation needed stronger stimulation intensity and was accompanied by several side effects including dizziness, nystagmus, and ipsilateral leaning compared to the SCP target. Shiro Horisawa et al. also reported a patient with generalized dystonia who responded well to SCP DBS than DN DBS [16]. The study reported by Brown et al. showed the validity of DN DBS in treating hemidystonia; however, it is worth noting that the active contacts were in close proximity to or within SCP [17].

DN and SCP are both important nodes in the cerebellum pathways that are connected to the brain. The DN receives ascending projections from the spinocerebellar tract as well as the premotor and supplementary motor cortices and integrates them. Its efferent projections travel through the SCP to the red nucleus, the thalamus, the basal ganglia, and other structures and subsequently transfer modulating signals to those regions [19]. Thus, the proximity of SCP to the downstream regions of DN may be of advantage for SCP stimulation to exert a better effect than DN stimulation but further examination is needed to confirm this. In addition, DN is the largest deep cerebellar nuclei that is approximately 13 mm to 23 mm in length, 7 mm to 20 mm in height, and 9 mm to 20 mm in width, [20] which is significantly larger than a DBS electrode [21]. The deviation of electrode placement in DN stimulation due to the large size of the DN may account for the variable effects observed in those reported cases and in our case.

The stimulation parameters (1.85~2.45 V, 50 µs, 130 Hz) used in this study were lower than most previously reported stimulation parameters of cerebellar DBS studies (Table 4) [13, 14, 15, 16, 17, 18]. The selection of the electrode lead and correct lead placement may be the key step for the low parameter in our study. In a previous report, [16] a 3387 lead (Medtronic, 1.5 mm contacts) was used and a very high stimulation (8.0 V, 150 µs, 200 Hz) was needed to achieve any clinical effect. Here, we selected an electrode with four longer lead contacts (3 mm), which may result in a much larger stimulation area and allow stimulation at increasing intensity and density [22]. In addition, our contacts on the SCP were near the midbrain, and electrodes were positioned across both the SCP and DN to allow optimal target programming. The active contacts within SCP were about 10 mm in length, thus 3387 lead alone may also be enough for SCP stimulation. Future studies should test the potential advantages of SCP in treating dystonia and address the underlying mechanisms.

Although our study has demonstrated the potential role of SCP DBS in improving the refractory symptoms of dystonia and spasticity in CP compared to conventional treatment, these results should be interpreted with caution. First, our patient had a history of hypoxia at birth, which may result in altered brain anatomy, though the cerebellum appeared intact on MRI. Second, the patient experienced SPR and GPi DBS, which might have altered he anatomy of her nervous system. In addition, this study only involved one patient and the etiology, age, and movement disorder progression can vary greatly between patients. Therefore, further studies are needed to elucidate the effects of SCP DBS for patients with CP.