Unusual idiopathic normal pressure hydrocephalus patient with marked asymmetric and upper body parkinsonism.

Asymmetry of parkinsonian symptoms is strong evidence toward the diagnosis of Parkinson's disease (PD). Lower body parkinsonism is characteristic in idiopathic normal pressure hydrocephalus (INPH). We report an unusual INPH patient with marked asymmetric and upper body parkinsonism. An 83-year-old man presented with gait impairment and asymmetric clumsiness of movement. According to the Unified Parkinson's Disease Rating Scale (UPDRS), the motor subscore was 12 in the left limb and 8 in the right. The score was 14 for both the upper and lower body. After the cerebrospinal fluid tap test (CSFTT), he showed marked improvement in the upper body score. A loss of asymmetry of parkinsonian signs, with greater improvement in the left limb, was presented. Fluorinated N-3-fluoropropyl-2β-carbomethoxy-3β-(4-iodophenyl)-nortropane (F-18 FP-CIT) positron emission tomography (PET) imaging was normal. In the differential diagnosis of elderly patients presenting with parkinsonism compatible with PD, we might need to consider a diagnosis of INPH.

Introduction

Idiopathic normal pressure hydrocephalus (INPH) is a treatable neurological disorder in the elderly involving nonobstructive enlargement of the cerebral ventricles in combination with one or more symptoms of cognitive impairment, gait disturbance, and urinary dysfunction.[1] The cerebrospinal fluid tap test (CSFTT) has been regarded as a valuable tool for diagnosis and the prediction of shunt effectiveness in patients with INPH.[1] Because of the treatable nature of INPH, diagnosis of patients potentially benefitting from CSF shunt surgery is important.

The Unified Parkinson's Disease Rating Scale (UPDRS) is well-known as the gold standard for evaluating motor symptoms in Parkinson's disease (PD) and provides a semiquantitative analysis of motor impairment.[2] Parkinsonian motor deficits have been also assessed with the UPDRS in other neurodegenerative diseases such as Alzheimer's disease (AD).[2] Most clinicians and researchers have used the UPDRS scale to determine the standard of response in some interventions for parkinsonian patients.

Diagnosis of INPH can often be ambiguous because of varying combinations or degrees of each of the classic clinical elements and overlap with symptoms of other common disorders in the elderly such as PD.[3] Parkinsonism is sometimes observed in patients with INPH.[4] In fact, in one report, INPH is described as shunt-responsive parkinsonism.[4] However, the detailed features of parkinsonian signs in INPH have been rarely described.[4] And, to the authors' knowledge, their changes on the UPDRS following the CSFTT have not yet been reported.

We report an INPH patient with marked asymmetric and upper body parkinsonism. We used the UPDRS III score as a means of analyzing parkinsonian signs and their severity. The patient showed evident improvement in his unusual parkinsonian symptoms after the CSFTT.

Case Report

An 83-year-old man presented to our hospital for evaluation of progressive slowness of movement and impairment of gait. Twelve months earlier, he had developed a short-stepped gait. Since then, he had complained of asymmetric clumsiness of movement, predominating in the left hemibody, and difficulty with performing precision movements such as buttoning his shirt. He had suffered from kinetic tremor bilaterally in the arms. His wife reported that his face had become expressionless. She also described a 6-month gradual decline in his ability to express himself and difficulties in carrying out complex tasks. He developed urinary urgency without leakage.

On initial examination, the patient's cognitive function was impaired (Korean Mini-Mental State Examination (K-MMSE) score 15 out of 30 and Clinical Dementia Rating Scale 2). Formal neuropsychological evaluation showed a deficit in attention (digit span test), visuospatial function (copy of the Rey-Osterrieth Complex Figure) and memory (Korean Hopkins Verbal Learning Test and recall and recognition of the Rey-Osterrieth Complex Figure) with frontal dysfunctions (Frontal Assessment Battery).

An experienced neurologist, who was blinded to the patient's diagnosis, rated the motor and gait performances. The patient had a masked face. There was a mild action tremor affecting both hands, in addition to mild-to-moderate bradykinesia, especially for rapid alternating movements. The patient had rigidity in the limbs and neck. He exhibited a short-stride gait with stooped posture, shuffling steps, reduced arm swing, and festination. His postural reflexes were markedly impaired. The initial UPDRS III score was 39. We also used the following subscores based on the UPDRS III: Global bradykinesia score, global rigidity score, upper body score, lower body score, right score, left score, and postural instability/gait difficulties score [Table 1].[567] Upper body parkinsonism was remarkable for an INPH patient (14 for upper body score and 14 for lower body score). His UPDRS score was 12 in the left limb and eight in the right. The postural instability/gait difficulties score was 11.

Table 1

Results of cerebrospinal fluid tap test

All laboratory test results, including thyroid function tests, vitamin B12 levels, and test for neurosyphilis, were unremarkable. Brain magnetic resonance imaging (MRI) revealed communicating hydrocephalus with an Evans' ratio of 0.34, and also showed CSF signal void in the cerebral aqueduct and enlargement of the temporal horns of the lateral ventricles [Figure 1a]. The principal diagnostic impression was INPH following the consensus criteria of Relkin et al.[3] However, based on the motor and gait examination findings of asymmetric parkinsonian symptoms and evident upper body parkinsonism, PD was also considered in the differential diagnosis of this patient. Fluorinated N-3-fluoropropyl-2β-carbomethoxy-3β-(4-iodophenyl)-nortropane (F-18 FP-CIT) positron emission tomography (PET) imaging showed normal dopamine transporter binding in the bilateral basal ganglia [Figure 1b].

Figure 1

(a) Brain magnetic resonance imaging; T2-weighted axial images showed the lateral ventricular enlargement with cerebrospinal fluid (CSF) signal void in the cerebral aqueduct. Thinning of the corpus callosum with enlargement of the temporal horns of the lateral ventricles was also demonstrated in T2-weighted coronal image. (b) Fluorinated N-3-fluoropropyl-2β-carbomethoxy-3β-(4-iodophenyl)-nortropane (F-18 FP-CIT) positron emission tomography imaging showed normal dopamine transporter binding in the bilateral basal ganglia.

A lumbar puncture with removal of 40 ml of CSF was performed. The CSF was clear and colorless with an opening pressure of 70 mmH2O. Before and after the spinal tap, he was evaluated using the INPH Grading Scale (INPHGS), K-MMSE, Timed Up and Go Test (TUG), and 10-m walking tests [Table 1]. Changes in gait were assessed repeatedly over 7 days after the tap, while changes in cognition and urination were evaluated at 1 week. The following criteria were used to decide the response of the CSFTT: Improvement of one point or more on the INPHGS, more than 10% improvement in time on TUG, or more than 3 points improvement on the K-MMSE.[1] He showed evident improvement by these criteria, and was judged as a responder [Table 1].

The UPDRS III was applied again 24 h after tap [Table 1]. His UPDRS III score decreased by 15%. He also showed more than 20% improvement in global bradykinesia score, global rigidity score, lower body score, and upper body score. Furthermore, the asymmetry of parkinsonian signs disappeared (13% reduction in right score and 33% reduction in left score).

Discussion

We present a unique patient with INPH. To the authors' knowledge, this is the first report of asymmetric and marked upper body parkinsonism as the presenting clinical feature of INPH. INPH is a surgically treatable neurological syndrome, and it should therefore be considered in the differential diagnosis of elderly patients presenting with parkinsonian symptoms.

PD is known as the most common type of parkinsonism, especially in elderly patients. In general, asymmetry of the parkinsonian features is considered as strong evidence toward a diagnosis of PD. A careful clinical evaluation revealing asymmetry of symptoms and signs has been known as the one of the best methods for differentiating PD from other parkinsonian diseases such as INPH.[8] However, another potential explanation of asymmetry is that the right hemisphere has undergone greater age-related decline compared to the left hemisphere, according to the right hemi-aging model.[9] Asymmetric brain atrophy has been reported in AD patients, and this asymmetry seemed to contribute to symptoms.[10] Additionally, in a report on INPH cases, most of them were also known to have AD pathology, and the comorbidity of such pathology has been shown to have great influence on the symptomatology of INPH.[11] In this context, our patient might show an asymmetric presentation of PD features that was characterized as more severe disease on the left side of the body.

Additionally, marked upper body parkinsonism was observed, and the motor subscores were same in our case for the upper and lower body. Generally, lower body parkinsonism is characteristic in INPH. However, gait disturbances, the most commonly reported symptoms of INPH, are known to be connected to frontal dysfunctions and microstructural damages in frontal lobe white matter regions.[12] And, frontal-subcortical circuits link basal ganglia with regions of the frontal lobe and thalamus, and are also known to regulate upper limb function.[13] Additionally, white matter lesions have a significant influence on facial expression, bradykinesia, and rigidity.[14] This potentially might help explain the upper body parkinsonism observed in our patient.

Both clinical and MRI findings were compatible with INPH in our case. Moreover, his PET imaging represented a condition not involving nigrostriatal neurodegeneration, which supported the diagnosis of INPH rather than PD. We tried to enhance diagnostic accuracy with comprehensive evaluation before and after the CSFTT by using various and objective grading scales and repeatedly evaluated change in gait over 7 days.

Clinical improvement after the CSFTT is regarded as an important feature that enhances diagnostic certainty from possible to probable in the Japanese guideline.[1] And shunt surgery is indicated for probable INPH, according to this guideline.[1] Removal of CSF in INPH patients might result in enhanced function of the frontal motor areas.[15] Moreover, not only gait patterns but also finger motor performance can improve after CSF removal.[15] Interestingly, our INPH patient showed marked improvement in the various subscores of UPDRS (especially in the global bradykinesia score, global rigidity score, and upper body score). According to the criteria defined in the previous study,[7] after CSF removal an obvious loss of asymmetry of parkinsonian signs, with the greater improvement in the more affected side, was presented in our case. Although these improvements in our patient further imply that the distinct asymmetric and upper body parkinsonism might be caused by INPH, no previous study has directly analyzed the change of UPDRS motor score after CSF removal.

This is an interesting report of an INPH patient presenting with unusual asymmetric and upper body parkinsonism, who showed obvious improvement in both symptoms after the CSFTT. In the differential diagnosis of elderly patients presenting with parkinsonism compatible with PD, we might need to consider a diagnosis of INPH after careful clinical examination.