
==== Front
J Neurosurg Case Lessons
J Neurosurg Case Lessons
J Neurosurg Case Lessons
Journal of Neurosurgery: Case Lessons
2694-1902
American Association of Neurological Surgeons

39250835
10.3171/CASE2429
CASE2429
HydrocephalusHydrocephalusTechniqueTechniqueDiagnostic-TechniqueDiagnostic TechniqueCase Lesson
Levodopa-resistant parkinsonism developing after ventriculoperitoneal shunting for obstructive hydrocephalus and improving after endoscopic third ventriculostomy, with specific consideration of brainstem morphology: illustrative case
Morisue Yoshihiko MD 1
Osawa Shin-ichiro MD, PhD 1
Niizuma Kuniyasu MD, PhD 12
Kanno Shigenori MD, PhD 3
Suzuki Kyoko MD, PhD 3
Endo Hidenori MD, PhD 1
1 Departments of Neurosurgery, Tohoku University School of Medicine, Sendai, Japan
2 Departments of Behavioral Neurology and Cognitive Neuroscience, Tohoku University School of Medicine, Sendai, Japan
3 Department of Neurosurgical Engineering and Translational Neuroscience, Graduate School of Biomedical Engineering, Tohoku University, Sendai, Japan
Correspondence Shin-ichiro Osawa: Tohoku University Graduate School of Medicine, Sendai, Miyagi, Japan. osawa@nsg.med.tohoku.ac.jp.
INCLUDE WHEN CITING Published September 9, 2024; DOI: 10.3171/CASE2429.

Disclosures The authors report no conflict of interest concerning the materials or methods used in this study or the findings specified in this paper.

09 9 2024
09 9 2024
8 11 CASE242909 1 2024
13 6 2024
© 2024 the authors
2024
the authors
https://creativecommons.org/licenses/by-nc-nd/4.0/ CC BY-NC-ND 4.0 (http://creativecommons.org/licenses/by-nc-nd/4.0/)

BACKGROUND

Parkinsonism has been reported in patients with obstructive hydrocephalus (OH) following ventriculoperitoneal shunting (VPS). While levodopa works well, some cases are drug resistant. A few case series have reported that endoscopic third ventriculostomy (ETV) is beneficial, though its mechanism remains unclear. The use of a pathophysiology-reflected marker can aid in the diagnosis and treatment strategy. The authors report a case of parkinsonism due to OH after VPS that improved after ETV in a patient taking levodopa, which was subsequently discontinued.

OBSERVATIONS

A 52-year-old man who had undergone VPS for OH caused by aqueductal stenosis with a tectal tumor presented with severe consciousness disturbance due to acute hydrocephalus and levodopa-refractory parkinsonism after multiple episodes of shunt malfunction. Magnetic resonance imaging showed an elevation of the floor of the third ventricle. ETV was performed to stabilize the pressure imbalance across the stenosis, and his parkinsonism symptoms improved after long-term rehabilitation, resulting in levodopa discontinuation. His pontomesencephalic angle, the angle between the anterior surface of the midbrain and upper surface of the pons in the midline of the sagittal plane, was significantly decreased.

LESSONS

The focus in such cases should be on the essence of the pathophysiology for improving the symptoms rather than on easy-to-understand indicators such as ventricle size.

https://thejns.org/doi/10.3171/CASE2429

parkinsonism
obstructive hydrocephalus
endoscopic third ventriculostomy
pontomesencephalic angle
case report
ABBREVIATIONS

CSF = cerebrospinal fluid
CT = computed tomography
ETV = endoscopic third ventriculostomy
EVD = external ventricular drainage
FTV = floor of the third ventricle
MRI = magnetic resonance imaging
OH = obstructive hydrocephalus
PMA = pontomesencephalic angle
UPDRS-III = Unified Parkinson’s Disease Rating Scale Part III
VPS = ventriculoperitoneal shunting.
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pmcParkinsonism has been reported to develop in patients with obstructive hydrocephalus (OH) after ventriculoperitoneal shunting (VPS),1, 2 and levodopa is effective in 65%–82% of such patients.1, 2 However, some patients can develop levodopa resistance, and several studies have reported improvements in the symptoms of parkinsonism after endoscopic third ventriculostomy (ETV).3–5 The mechanism by which ETV improves parkinsonism is not well understood. Here, we present a case of severe parkinsonism accompanied by OH that improved after ETV. The anatomical change in the brainstem proposes an index to quantify the pathophysiological mechanism of parkinsonism.

Illustrative Case

A 48-year-old man presented with fluctuating disorders of consciousness, binocular dysfunction (vertical gaze palsy, diplopia, and convergence insufficiency), and gradually emerging parkinsonism (akinesia and rigidity in all 4 limbs, Unified Parkinson’s Disease Rating Scale Part III [UPDRS-III] score 64) 25 years after VPS for OH. His parkinsonism was treated with levodopa 450 mg a day, but he showed only a partial response to the treatment. Over the following years, his hydrocephalus repeatedly worsened and was accompanied by altered consciousness and enlarged ventricles due to shunt malfunction, resulting in multiple shunt revisions. At 52 years of age, he developed severe altered consciousness due to acute hydrocephalus with shunt malfunction, which was the seventh occurrence in the past 4 years. He underwent external ventricular drainage (EVD), and his consciousness disturbance improved within several days. However, his parkinsonism remained and worsened to the point where he became bedridden and totally dependent in activities of daily living (Hoehn-Yahr stage V, UPDRS-III score 77) even after 2 weeks following EVD. The levodopa dosage was increased to 800 mg per day, but he had no improvement. Head computed tomography (CT) revealed a calcified lesion in the dorsal midbrain (Fig. 1B), consistent with a low-grade glioma in the tectum. Magnetic resonance imaging (MRI) revealed an obstruction of the aqueduct, enlargement of the third ventricle, and elevation of the floor of the third ventricle (FTV; Fig. 1A and C), showing an imbalance of cerebrospinal fluid (CSF) pressure between the third ventricle and prepontine cistern. We confirmed that the shunt pressure change did not work and determined that the seventh shunt malfunction had occurred. FIG. 1. A: Preoperative head CT scan shows a tectal tumor with calcification. B: Preoperative axial T2-weighted MRI shows enlargement of the lateral and third ventricles. The Evans index is 0.30. C: Preoperative sagittal heavily T2-weighted MRI shows an elevation of the FTV.

We hypothesized that the unstable condition in the present case was caused by 2 interrelated mechanisms. The first mechanism was the CSF pressure gradient between the third ventricle and the cistern, which was reflected in the elevation of the FTV. The other mechanism was overdrainage from the closed CSF space by VPS. It was difficult to avoid both overdrainage and the aggravation of hydrocephalus with lower ventricular reserve for CSF volume, a condition known as “slit ventricle syndrome.” We performed ETV to improve both of the abovementioned conditions. EVD dependency did not improve even after ETV; therefore, we performed a VPS revision, considering the CSF malabsorption. The patient’s unstable consciousness improved and stabilized in the early postoperative period, but his parkinsonism did not improve. After long-term rehabilitation lasting 6 months, he showed significant improvement in his parkinsonism and returned to his job (Hoehn-Yahr stage I, UPDRS-III score 15), and the treatment with levodopa was discontinued. Follow-up MRI 2 years after surgery showed no change in the ventricle size, but an improvement in the elevation of the FTV was seen (Fig. 2). The pontomesencephalic angle (PMA), which is the angle between the anterior surface of the midbrain and the superior surface of the pontine in the midline of the sagittal plane, decreased from 67° to 52° after ETV (Fig. 3). FIG. 2. A: Postoperative axial T2-weighted MRI shows an improvement in the dilation of the lateral and third ventricles. The Evans index is 0.29. B: Postoperative sagittal heavily T2-weighted MRI confirms the presence of a fenestrated FTV and shows that the floor descends accordingly.

FIG. 3. The PMA is the angle between the two red lines, which was 67° preoperatively (A) and 52° postoperatively (B), as demonstrated on heavily T2-weighted MRI.

Patient Informed Consent

The necessary patient informed consent was obtained in this study.

Discussion

In this paper, we present a case of levodopa-resistant parkinsonism that developed after VPS for OH and improved after treatment with ETV. After a long-term rehabilitation period of 6 months following ETV, the patient showed a marked improvement in his symptoms, and levodopa was discontinued. The morphological change in the brainstem was most prominent in the sagittal view, with a quantitative difference in the PMA.

Observations

Parkinsonism associated with hydrocephalus is a common comorbidity in patients with normal pressure hydrocephalus (62%–86%).6–8 The frequency of parkinsonism in patients with OH is unclear, but several reports on such cases have been published.9–16 Furthermore, in several cases of parkinsonism, the symptoms manifested after VPS for OH.1–10, 17–30 Among the several mechanisms in the development of parkinsonism after VPS for OH, 2 valid hypotheses have been proposed.1 One hypothesis points to the disturbance of the presynaptic nigrostriatal dopaminergic pathway, that is, reduced dopamine uptake in the striatum, resulting in parkinsonism. The hypothesis includes impaired blood flow to the striatum due to enlargement of the lateral and third ventricles3, 9 and mechanical compression of the striatum and substantia nigra.9, 31 The hypothesis could be applied to most cases of parkinsonism occurring after VPS for OH because the pathophysiology was supported by the fact that levodopa and other antiparkinsonism medications are often effective.3, 4, 9, 10, 21, 23–25, 32 The other hypothesis points to a disorder of the corticobasal ganglia loop. This differs from the former hypothesis, as it is not associated with damage to the nigrostriatal dopaminergic neurons but with damage to the frontal cortex4 and corpus callosum,32 which consist of the loop. This type of parkinsonism was considered to be levodopa resistant and is associated with brainstem dysfunction and impaired blood flow to the frontal cortex and corpus callosum due to physical stress and the anatomical deformity associated with ventricular enlargement.4, 32 This pathophysiology is considered to be resistant to levodopa, but ETV can be effective for this condition.3–5 The increase in pressure from the lateral to third ventricle due to OH can be more acute and severe than that due to communicating hydrocephalus, which is consistent with the clinical course of the present case.

There are several studies reporting an improvement in parkinsonism in patients who developed parkinsonism after VPS for OH and who were treated with ETV (Table 1).3–5, 19 Although several studies have described the anatomical changes around the FTV before and after ETV,10, 33, 34 no report has mentioned the significance of how the FTV became deformed. Here, we present the size of the PMA as an alternative marker that represents the severity of the pressure gradient induced by CSF drainage from the isolated ventricle after VPS. In the present case, sagittal MRI showed significant quantitative changes in the PMA. The utility of the PMA measurement was first reported in cases of intracranial hypotension,35, 36 where the PMAs in the pathology groups were more acute than those in the control groups. The PMAs in the control groups were documented as 56.27° ± 8.9°35 and 61.0° ± 6.1°36 (mean ± standard deviation). Recently, Demir et al.37 reported that the PMA in healthy Turkish males was 56.77° ± 9.78°. Though the reported values of the PMA varied among studies, the preoperative PMA of our case was 67°, which is higher than the mean value of previously reported cases. We also considered that the corrected pressure gradient between the third ventricle and prepontine cistern by ETV restored the brainstem’s structural deformity, which could contribute to the improvement in parkinsonism. This consideration is concordant with the fact that the patient’s parkinsonism was levodopa resistant, that improvement of symptoms took a longer time after ETV, and that finally he discontinued the levodopa treatment. TABLE 1. Cases of parkinsonism with OH occurring after VPS followed by ETV

Authors & Year	Age at ETV (yrs)	Sex	Etiology	Parkinsonism	
Outcome	Time to Improvement	Levodopa After ETV	
Kinugawa et al., 20093	49	M	Unkown	Improved	NA	Continued	
Hashizume et al., 20114	47	F	Unkown	Improved	2 mos	Discontinued	
Okawa et al., 20155	51	M	AS due to IVH	Improved	6 wks	Continued	
Shpiner et al., 202117	35	M	Unknown	Unchanged	NA	Unknown	
Present case	52	M	Tectal tumor	Improved	6 mos	Discontinued	
AS = aqueductal stenosis; IVH = intraventricular hemorrhage; NA = not accessible.

In this report, we applied the PMA as a characteristic of parkinsonism in patients with OH that improved after treatment with ETV. We propose that the PMA can be a quantitative marker reflecting the pathophysiology of parkinsonism that develops following VPS for OH and possibly predicting whether ETV is beneficial or not. However, our study reports a single case, so further investigation of a large sample is required to clarify whether the PMA is a useful predictor of the effectiveness of ETV as treatment for patients with parkinsonism along with OH or other types of hydrocephalus.

Lessons

We report a case of levodopa-refractory parkinsonism that developed after VPS for OH and improved after ETV. The PMA quantified the morphological change of the brainstem before and after ETV. We should focus on the essence of the pathophysiology for improving the symptoms rather than on easy-to-understand indicators such as ventricle size.

Disclosures

The authors report no conflict of interest concerning the materials or methods used in this study or the findings specified in this paper.

Author Contributions

Conception and design: Osawa, Morisue. Acquisition of data: Osawa, Morisue, Niizuma, Kanno, Suzuki. Analysis and interpretation of data: Osawa, Morisue, Suzuki. Drafting the article: Osawa, Morisue. Critically revising the article: Osawa, Niizuma. Reviewed submitted version of manuscript: Osawa, Niizuma. Approved the final version of the manuscript on behalf of all authors: Osawa. Study supervision: Suzuki, Endo.

Correspondence

Shin-ichiro Osawa: Tohoku University Graduate School of Medicine, Sendai, Miyagi, Japan. osawa@nsg.med.tohoku.ac.jp.
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