Reply to the comments on “Unusual case of idiopathic normal pressure hydrocephalus initially presenting as Parinaud’s syndrome?”

Abstract

We are grateful to Dr Onder for the comments on our case report, “Unusual case of idiopathic normal pressure hydrocephalus initially presenting as Parinaud’s syndrome.” Below are our responses to the comments. With regard to the first comment that pure upward gaze palsy without dorsal midbrain lesion makes the diagnosis of Parinaud’s syndrome (PS) doubtful, we disagree with this opinion. We believe that PS could be regarded as a clinical syndrome with a cluster of abnormalities of eye movement and pupil dysfunction, and the pathophysiology of PS is thought to be induced by dorsal midbrain dysfunction regardless of any specific lesion. We deduced that normal pressure hydrocephalus (NPH)-induced compressive effect affecting the dorsal midbrain might result in upward gaze palsy and ptosis of the patient. Characteristic neuroophthalmological findings in PS consist of vertical gaze palsy, especially upward rather than downward; pupillary light-near dissociation; convergence-retraction nystagmus; and lid retraction. However, as aforementioned in the letter of Dr Onder, it was found that the classical triad of PS was only present in 65% of cases in a recent crucial review. Pollak et al. defined PS as showing one or more of the following signs: limitation of upgaze, pupillary light-near dissociation or convergence-retraction nystagmus. In this literature, the full picture of PS was present in 27% of patients, and the following patients were regarded as having PS: two patients showing only pupillary light-near dissociation; and two other patients with pure convergence-retraction nystagmus. Also, Rojas et al. reported a patient with minimal anomalies of PS showing slowed upward saccades and pupillary light-near dissociation in the absence of upgaze palsy, convergence-retraction nystagmus, and lid retraction. Additionally, the present patient had not only upward gaze palsy, but also ptosis, which could be observed in PS. As a consequence, we concluded that the phenomenology of the present case was highly compatible with PS. We could understand the Author’s concern, which points out the possibility of dual pathology of progressive supranuclear palsy (PSP) with idiopathic NPH, and neurodegenerative NPH (distinct from idiopathic NPH) as a presenting feature of PSP. However, upgaze palsy only is extremely rare, and slowing of downward or horizontal saccades appears in the early stage of PSP with ocular motor dysfunction. In the present patient, downward and horizontal saccades/pursuits were unremarkable. In addition, according to the new diagnostic criteria of PSP revised in 2017, typical neuroimaging features suggestive of idiopathic NPH make the diagnosis of PSP highly unlikely. Dramatic response of upward gaze palsy to ventriculoperitoneal shunt operation (Video S1) also strongly supports that PS was induced by idiopathic NPH. For the last comment, demonstration of postsynaptic striatal dopaminergic degeneration using functional imaging is not mandatory, but supportive for the diagnosis of PSP in the revised crietria. Several articles were published investigating the role of F-fluorinated-N-3-fluoropropyl-2-β-carboxymethoxy3-β-(4-iodophenyl)nortropane (F-FP-CIT) positron-emission tomography (PET) as a potential diagnostic modality for PSPRichardson’s syndrome. Although there is little data about the utility of dopamine imaging in variant PSP, a few studies reported that dopamine imaging could be sensitive for variant PSP, as well as PSP-Richardson’s syndrome. Furthermore, Yoo et al. recently showed that F-FP-CIT PET could be used for the diagnosis of PSP (including PSP-Richardson’s syndrome and variant PSP) at early stages of the disease. Hence, the absence of dopaminergic depletion using F-FP-CIT PET might contribute to the patient’s diagnosis in this case. Clinical features of PS without downward gaze palsy commonly seen in PSP, typical neuroimaging features of idiopathic NPH, dramatic response to ventriculoperitoneal shunt operation and the absence of dopaminergic depletion on F-FP-CIT PET led us to the conclusion that clinical diagnosis of PSP was inappropriate in the present case. Furthermore, after the ventriculoperitoneal shunt operation, the patient has been well for a year without any worsening of neurological deficits. Collectively, we concluded that the patient showed shunt-responsive PS without dorsal midbrain lesion.