There are a variety of neurodegenerative diseases that require differentiation from idiopathic normal pressure hydrocephalus, including Alzheimer's disease, Parkinson's disease, dementia with Lewy bodies, frontotemporal dementia, progressive supranuclear palsy, corticobasal degeneration. As the clinical features and structural imaging findings of these diseases may overlap with iNPH, biomarkers reflecting disease-specific pathology are necessary for differential diagnosis. In addition, these diseases often coexist with iNPH in elderly patients, and it is important to confirm the coexistence of their pathology even in cases clinically diagnosed as iNPH 1).
Multiple other illnesses may present similarly to normal pressure hydrocephalus (NPH) that should be considered in the Differential diagnosis. In particular, Parkinson's disease and NPH may present in a similar, but distinct manner. Start hesitation and freezing episodes can occur in NPH, often mimicking the gait in Parkinson's disease. In contrast to Parkinson's disease, rigidity and unilateral rest tremor are less commonly observed. Furthermore, a robust response to L-Dopa is not typically seen in NPH, in contrast to Parkinson's disease.
Many elderly people suffer from combined motor and cognitive dysfunction (and sometimes from incontinence as well). Moreover, three-quarters of patients with (i)NPH simultaneously have vascular or Alzheimer’s dementia. Thus, the differential diagnosis of NPH can be quite difficult. Findings that make the diagnosis of NPH less likely include the following:
Intracranial pressure above 25 cm H2O (this rules out iNPH, by definition) Age under 40 (iNPH unlikely) Asymmetrical or transient symptoms Cortical deficits, e.g., aphasia, apraxia, or paresis Progressive dementia without gait disturbance (even if the ventricles are enlarged) Lack of progression of symptoms (a controversial point, as authors differ on the period of time in which symptoms should be seen to progress). The differential diagnosis of gait disturbances includes peripheral neuropathy, spinal canal stenosis, disorders of the inner ear, chronic alcoholism, and deficiencies of vitamin B6 and B12 (2, e17, e18). The differential diagnosis of cognitive deficits includes various types of dementing disease (Table 2). It is often not possible to distinguish NPH from other causes of subcortical dementia by the clinical and radiological findings alone, so that further, invasive tests are needed (e17, e18, e20, e45).
Findings that make NPH less likely
Asymmetrical findings Cortical deficits, e.g., aphasia, apraxia, paresis Progressive dementia without gait disturbance Lack of progression of symptoms 2).
Secondary normal pressure hydrocephalus (NPH) does indeed exist and should be differentiated from idiopathic normal pressure hydrocephalus (iNPH) based on outcome as well as clinical, pathophysiological, and epidemiological characteristics but should not be considered as a separate entity.
Evaluation of patients with NPH to identify a known cause is recommended because the response to treatment varies considerably. Although clinical presentation is often the same, a multitude of primary etiologies can lead to the development of sNPH. The most common etiologies of sNPH include SAH, traumatic brain injury, intracranial malignancies, meningitis, and stroke. Further studies are required to investigate differences in management and outcome among the diverse etiologies of sNPH 3).
In Alzheimer's disease (AD) patients, diffuse aggregates of amyloid-β (Aβ) and neurofibrillary hyperphosphorylated tau are detected in the neocortex of the brain, while similar accumulation of Aβ is also detected in iNPH.
Apolipoprotein E (APOE4) affects the Aβ deposition in the brain of iNPH and AD patients in a similar manner 4).
APOE4 is not a risk factor for iNPH and does not predict the response to shunt. Data further support the view that the iNPH syndrome is a distinct dementing disease 5).
Espay et al. summarize the long-term institutional experience, in which post-shunt benefits in patients with initial diagnosis of idiopathic NPH persist in only 32% of patients at 36 months, with known revised diagnosis in over 25% (Alzheimer disease, dementia with Lewy bodies, and progressive supranuclear palsy. They postulate that previously reported NPH cases with “dual” pathology (i.e., developing a “second” disorder) more likely represent ventriculomegalic presentations of selected neurodegenerative disorders in which benefits from shunting may be short-lived, with a consequently unfavorable risk-benefit ratio 6).
Patients with shunt-responsive INPH showed higher Fractional Anisotropy (FA) in the posterior limb of the internal capsule compared with healthy controls and those in other groups of dementia that was reversible with shunt surgery. With this parameter, shunt-responsive INPH could be distinguished from AD, subcortical vascular dementia, and healthy conditions with high diagnostic accuracy 7).
Neurodegenerative disorders
● see Alzheimer’s disease differential diagnosis
● progressive supranuclear palsy
● amyotrophic lateral sclerosis
Vascular dementia
● CADASIL
● vertebrobasilar insufficiency (VBI)
Other hydrocephalic disorders
● long-standing overt ventriculomegaly syndrome
● noncommunicating hydrocephalus
Infectious disease
● HIV
● syphilis
Urological disorders
● bladder cancer or prostate cancer
● benign prostatic hyperplasia (BPH)
Miscellaneous
● epilepsy