Idiopathic normal pressure hydrocephalus (iNPH) is a progressive neurodegenerative disease in the elderly with enlarged ventricles and normal or slightly elevated cerebrospinal fluid pressure, clinically characterized by an insidious onset and gradual progression of impairments of gait, balance, cognition, with urinary incontinence 1).
Normal Pressure Hydrocephalus first became recognized on March 10, 1964 as a distinct medical syndrome by Salomón Hakim, M.D., Ph.D.
The classic triad of magnetic apraxia, urinary incontinence, and dementia remain relevant into the 21(st) century as being the basis for symptomatic diagnosis and predicting potential benefit from cerebrospinal fluid shunting, though they have been greatly augmented by the addition of modern neuroimaging, particularly MRI.
Modern criteria recognize a wider range of diagnostic criteria, and new positive and negative prognostic indicators for treatment benefit have been discovered, though the mainstay remains initial drainage of a large volume of cerebrospinal fluid and monitoring for clinical improvement. Even with our advances in understanding both primary and secondary normal pressure hydrocephalus, diagnosis, management, and counseling remain challenging in this disorder 2).
It is predominantly a disease of the elderly. By its nature, many of those who present to clinic are in advanced old age with multiple comorbidities. Majority of patients treated are younger than 80 years old.
It occurs most frequently in the 70s, gait impairment and cognitive decline are the most frequent initial symptoms in men and women, respectively, and hypertension and diabetes are the most frequent comorbidities in men and women, respectively 4).
In people over 65 years old, pooled prevalence obtained from specific population studies was 1.3%, almost 50-fold higher than that inferred from door-to-door surveys of dementia or Parkinsonism. Prevalence may be even higher in assisted-living and extended-care residents, with up to 11.6% of patients fulfilling the criteria for suspected iNPH and 2.0% of patients showing permanent improvement after cerebrospinal fluid (CSF) diversion. The only prospective population-based survey that reported iNPH incidence estimated 1.20 cases/1000 inhabitants/year, 15-fold higher than estimates obtained from studies based on hospital catchment areas. The incidence of shunt surgery for iNPH and SRiNPH obtained from incident cases of hospital catchment areas appears to be fewer than two cases and one case/100,000 inhabitants/year, respectively. Unfortunately, there is no population-based study reporting the real values for these two parameters.
The prevalence of iNPH, in Japan among people older than 65, the prevalence is between 0.5% and 2.9% 5) and the syndrome is both underdiagnosed and undertreated.
It is recommended that INPH be classified into probable, possible, and unlikely categories. It is hope that these criteria will be widely applied in clinical practice and will promote greater consistency in patient selection in future clinical investigations involving INPH 6).
All patients with idiopathic normal pressure hydrocephalus (INPH) who underwent shunting in Sweden in 2008-2010 were compared to age- and sex-matched population-based controls. Inclusion criteria were age 60-85 years and no dementia. The 10 most important vascular risk factor (VRFs) and cerebrovascular and peripheral vascular disease were prospectively assessed using blood samples, clinical examinations, and standardized questionnaires. Assessed VRFs were hypertension, hyperlipidemia, diabetes, obesity, psychosocial factors, smoking habits, diet, alcohol intake, cardiac disease, and physical activity.
In total, 176 patients with INPH and 368 controls participated. Multivariable logistic regression analysis indicated that hyperlipidemia (odds ratio [OR] 2.380; 95% confidence interval [CI] 1.434-3.950), diabetes (OR 2.169; 95% CI 1.195-3.938), obesity (OR 5.428; 95% CI 2.502-11.772), and psychosocial factors (OR 5.343; 95% CI 3.219-8.868) were independently associated with INPH. Hypertension, physical inactivity, and cerebrovascular and peripheral vascular disease were also overrepresented in INPH. Moderate alcohol intake and physical activity were overrepresented among the controls. The population-attributable risk percentage was 24%.
The findings confirm that patients with INPH have more VRFs and lack the protective factors present in the general population. Almost 25% of cases of INPH may be explained by VRFs. This suggests that INPH may be a subtype of vascular dementia. Targeted interventions against modifiable VRFs are likely to have beneficial effects on INPH 7).
Although the exact pathogenesis of NPH is unknown, many possible causes have been postulated, including cerebral ischemia. Studies have demonstrated that periventricular blood flow and cerebrovascular autoregulation are reduced.
It is also thought that biomechanical changes, such as the combination of tissue distortion caused by ventricular dilation, CSF and interstitial fluid stasis, and impaired autoregulation may result in failure of drainage of neurotoxic compounds such as Amyloid beta.
Increased CSF stroke volume through the aqueduct has also been demonstrated in the NPH population despite normal CSF pressures. The reaction of the cerebral mantle to all or some of these processes is poorly understood. It is thought that white matter tract connections serving the cortex could be disrupted in a variety of ways, including disconnection, swelling, stretching, and compression. Therefore, it is possible that some types of disruption may be more tolerable (i.e., more reversible) than others.
Only a few studies have seized the opportunity to reevaluate the theories of pathogenesis of NPH using developments in imaging techniques.
The disorders of Alzheimer disease, vascular dementia and normal pressure hydrocephalus are all causes of dementia in the elderly population. It is often the case that it is clinically very difficult to tell these diseases apart. All three forms of dementia share the same risk factors, which for the most part are vascular risk factors. Bateman proposes that there is an underlying vascular pathophysiology behind these conditions, which is related to the strength of the pulse waves induced in the craniospinal cavity by the arterial vascular tree. It is proposed the manifestation of the dementia in any one patient is dependant on the way that the pulsations interact with the brain and its venous and perivascular drainage. This interaction is predominately dependant on the compliance of the craniospinal cavity and the chronicity of the increased pulse wave stress 8).
Kaolin was injected bilaterally into the subarachnoid space overlying the cranial convexities in 20 adult rats. Magnetic resonance imaging (MRI) was obtained by using an 11.7 T scanner at 14, 60, 90, and 120 days after kaolin injection. Locomotor, gait, and cognitive evaluations were performed independently. Kaolin distribution and the associated inflammatory and fibrotic responses were histologically analyzed.
Evans index of ventriculomegaly showed significant progressive growth in ventricular size over all time points examined. The greatest enlargement occurred within the first 2 months. Evans index also correlated with the extent of kaolin distribution by MRI and by pathological examination at all time points. First gait changes occurred at 69 days, anxiety at 80, cognitive impairment at 81, and locomotor difficulties after 120 days. Only locomotor deterioration was associated with Evans index or the radiological evaluation of kaolin extension. Inflammatory/fibrotic response was histologically confirmed over the cranial convexities in all rats, and its extension was associated with ventricular size and with the rate of ventricular enlargement.
Kaolin injected into the subarachnoid space over the cerebral hemispheres of adult rats produces an inflammatory/fibrotic response leading in a slow-onset communicating hydrocephalus that is initially asymptomatic. Increased ventricular size eventually leads to gait, memory, and locomotor impairment closely resembling the course of human adult chronic hydrocephalus 9).
Disturbed cerebrospinal fluid (CSF) dynamics are part of the pathophysiology of normal pressure hydrocephalus (NPH).
A study investigated the contribution of established CSF dynamic parameters to mean pulse amplitude (AMP), a prognostic variable defined as mean amplitude of cardiac-related intracranial pressure pulsations during 10 min of lumbar infusion test, with the aim of clarifying the physiological interpretation of the variable. AMP(mean) and CSF dynamic parameters were determined from infusion tests performed on 18 patients with suspected NPH. Using a mathematical model of CSF dynamics, an expression for AMP(mean) was derived and the influence of the different parameters was assessed. There was high correlation between modelled and measured AMP(mean) (r = 0.98, p < 0.01). Outflow resistance and three parameters relating to compliance were identified from the model. Correlation analysis of patient data confirmed the effect of the parameters on AMP(mean) (Spearman's ρ = 0.58-0.88, p < 0.05). Simulated variations of ±1 standard deviation (SD) of the parameters resulted in AMP(mean) changes of 0.6-2.9 SD, with the elastance coefficient showing the strongest influence. Parameters relating to compliance showed the largest contribution to AMP(mean), which supports the importance of the compliance aspect of CSF dynamics for the understanding of the pathophysiology of NPH 10).
Elderly presenting with gait abnormality, cognitive decline, and urinary incontinence, with enlarged ventricles of the brain but normal or slightly elevated cerebrospinal fluid (CSF) pressure 11) 12).
Postural stability in NPH is predominantly affected by deficient vestibular functions, which did not improve after spinal tap test. Conditions which improved best were mainly independent from visual control and are based on proprioceptive functions 13).
The natural course of iNPH is symptom progression over time, with worsening in gait, balance and cognitive symptoms. This deterioration is only partially reversible.
Currently there is no pathological hallmark for iNPH 14).
It is frequently present with cerebral vasculopathy; significantly increased prevalence of cardiovascular disease iNPH patients, which provide evidence that cardiovascular disease is involved as an exposure in the development of iNPH 15).
Idiopathic normal pressure hydrocephalus (iNPH) may present, besides the classic triad of symptoms, extrapiramidal parkinsonian like movement disorders.
Management of idiopathic normal-pressure hydrocephalus (iNPH) is hard because the diagnosis is difficult and shunt surgery has high complication rates. .
Shunt surgery has been established as the only durable and effective treatment for idiopathic normal pressure hydrocephalus
To maximise the benefits of shunt treatment, surgery should be performed soon after diagnosis 16).
The results of a prospective multicentre study on patients with iNPH diagnosed solely on clinical and radiological criteria support shunt surgery in patients presenting with symptoms and signs and MRI findings suggestive of iNPH 17).
The only randomized trial of endoscopic third ventriculostomy (ETV) for idiopathic normal pressure hydrocephalus (iNPH) compares it to an intervention which is not a standard practice (VP shunting using a non-programmable valve). The evidence from this study is inconclusive and of very low quality. Clinicians should be aware of the limitations of the evidence. There is a need for more robust research on this topic to be able to determine the effectiveness of ETV in patients with iNPH 18).