Is DAT imaging abnormality in normal pressure hydrocephalus always suggestive of degeneration?

Abstract

Idiopathic normal pressure hydrocephalus (iNPH) is a debated entity with controversial pathogenesis, diagnostic criteria, and predictors of response after ventriculoperitoneal shunt (VPS). Parkinsonian signs are frequently reported in the clinical picture, sometimes due to the coexistence of an underlying neurodegenerative parkinsonism and sometimes in the absence thereof. To distinguish these two scenarios is crucial, since they may carry different long-term response to CSF drainage. 123 I-FP-CIT-SPECT was believed to be helpful in this regard, however its role in predicting surgical outcome has been disputed. We illustrate a patient presented with gait disturbance, urinary incontinence, and asymmetrical parkinsonian signs, who underwent a 3T brain MRI and a 123 I-FP-CIT-SPECT. VPS was performed. The patient repeated a 123 I-FP-CIT-SPECT, 18 months after the operation, and was clinically followed up for 24 months. Our patient displayed clinical and radiological criteria for iNPH and an abnormal asymmetrical uptake in 123 I-FP-CIT-SPECT, consistent with her asymmetrical parkinsonism. However, the organization of the substantia nigra studied with iron-sensitive sequences in 3T brain MRI scan appeared intact. The patient revealed an improvement both clinically and in 123 I-FP-CIT-SPECT at postsurgical follow-up. Our report suggests that abnormal 123 I-FP-CIT-SPECT may not necessarily reveal an overlap with neurodegenerative parkinsonism; its partial reversibility may suggest that the mechanical effect exerted on the striatum by ventriculomegaly ultimately leads to downregulation of dopaminergic transporters which may improve after VPS.

Parkinsonism in idiopathic normal pressure hydrocephalus: is it time for defining a clinical tetrad?

“…The results suggest that down-regulation of the postsynaptic D2 receptor could be related to a dysfunction of the cortico-striatal network due to hydrocephalus. This hypothesis on the mechanical effect exerted on the striatum by ventriculomegaly, which should be prominent in the caudate nucleus leading to the downregulation of dopaminergic transporters, has also been supported by single-photon emission computerized tomography (SPECT) studies [ 29 , 36 , 37 ]. In a recent paper striatal dopamine reuptake transporter density has been shown to differentiate iNPH patients with prevalent imbalance from those with major locomotor impairment, which also demonstrated a significant association between parkinsonism and striatal uptake only for the latter phenotype [ 38 ].…”

Parkinsonism and cerebrospinal fluid disorders

“…Surprisingly, some studies showed even a greater involvement in upper than lower extremities [14,19], and other authors described NPH patients with only upper limb parkinsonism [15,30]. The occurrence of bradykinesia and rigidity was not reported in the same body district by most of these studies [15,19,30]. As for rest tremor, it was seen mostly in the upper limbs [19,43,44], and only one patient had both upper and lower limb tremor [15].…”

“…Parkinsonism can be present from the early stages of NPH and may progress with time [28]. A previous study described parkinsonism in 55 NPH patients with a mean disease duration of only 8.8 months [29], and found lower scores of the motor section (part III) of the Unified Parkinson's Disease Rating Scale (UPDRS) compared to other studies enrolling NPH patients with longer mean disease durations (from 2.2 to 3.1 years) [17,19,30]. Many studies applied scales developed for PD, especially when comparing the clinical features among subjects with NPH or other parkinsonian disorders or when assessing changes after intervention [14,17,20].…”

“…In terms of body distribution, parkinsonism of the upper limbs has been reported in some studies [14,15,17,19,30,45]. Surprisingly, some studies showed even a greater involvement in upper than lower extremities [14,19], and other authors described NPH patients with only upper limb parkinsonism [15,30].…”

Differentiating comorbidities and predicting prognosis in idiopathic normal pressure hydrocephalus using cerebrospinal fluid biomarkers

“…Because of these overlapping features, it is not uncommon for individuals with idiopathic PD or secondary parkinsonism to be suspected of having concomitant iNPH. DAT imaging is believed to be helpful for this purpose, but as a possible explanation, the mechanical effect exerted on the striatum by ventriculomegaly ultimately downregulates dopaminergic transporters, which may improve after shunt ( 72 ). Comorbidity with atypical parkinsonian disorders ( 73 , 74 ), MSA, PSP, CBD, or LBD affects the long-term prognosis of shunting in wide-based gait with staggering walk, lateral instability executive dysfunction ( 59 ), and apathy within 3 years of the treatment.…”