- Background: Normal pressure hydrocephalus is a condition characterized by sphincteric incontinence, gait disturbance and dementia. It has been gaining deserved attention as its associated dementia is characterized by being reversible by a shunt procedure or surgery after which many patients symptoms resolved including improvement of their cognitive abilities. Unfortunately not all cases with suspected NPH improve after shunt operation. Therefore it is important to research investigations that would better correlate with post shunt outcome. Historically CSF tapping has been used for this purpose, but this is an invasive procedure that carries a significant risk of morbidity and even mortality. MRI applications may provide a non-invasive diagnosis of NPH and their correlation with shunt responsiveness has been the topic of research in the last few years. These applications includes MRCSF flowmetry or cine phase MRI, MR perfusion, diffusion and MR spectroscopy. This latter technique, MR spectroscopy (MRS), has been the topic of very few papers in recorded literature. Unfortunately, some of them are conflicting and are hard to compare for the purpose of reaching final recommendation about the use of MRS in the clinical practice as a non-invasive tool to predict responsiveness to shunting. As a matter of fact, MRS clinical usefulness has well established indications and benefits in the diagnosis of conditions such as “brain neoplasms, neonatal and pediatric disorders (hypoxia-ischemia, inherited metabolic diseases, and traumatic brain injury), demyelinating disorders, and infectious brain lesions.” Oz et al 2014 The purpose of this work is to identify and assess articles dedicated to this purpose to see whether we can determine the utility of MR Spectroscopy as a non-invasive tool to diagnose NPH and assess shunt responsiveness.
- Methods: A thorough review of the literature was performed On Ovid search engine selecting Embase 1980-2015 and Medline 1946 to 2015 databases. Languages of articles found were in English language and reference lists searches from full text articles. The same search strategy was reapplied to the Pubmed search engine. The key words used in our search strategy were (MRS or spectroscopy) and (NPH or normal pressure hydrocephalus). The results 149 entries, for which abstracts were analyzed for relevance and non-relevant entries were omitted. Furthermore, the reference list of relevant articles were also reviewed to make sure no relevant articles were left out.
- Results: Our aim was to find studies assessing Normal Pressure Hydrocephalus patients through Magnetic resonance spectroscopy. Intended inclusion criteria included, randomized controlled trials which used MRS to assess frontal deep white matter both pre and post CSF shunting procedures. Given the scarcity of the available literature, we could not exclude articles based on our preferred inclusion criteria, instead we noted all the deviations from these criteria that we found in those papers and we used them in our conclusion section where we try to pinpoint which criteria should be implemented in any future studies dealing with our topic. Using these criteria only seven articles were identified dealing with the topic of the role of MRS in assessing shunt responsiveness of patients with Normal Pressure Hydrocephalus. The date of their publication range from 2001 to 2012. Widely-varying techniques of image acquisition and processing were used. The sample size of all the studies was small ranging from 12 to 21 subjects, which considerably affects the generalization of their conclusion. Indeed each and every study concludes by calling for larger studies to be done to verify their results. Nevertheless, there is an evident line of progression in the results and conclusions of the studies over time. Indeed, current evidence highlights that the N Acetyl Aspartate to Creatine ratio (NAA/CR ratio) is decreased in the thalamus of NPH patients, which is now attributed to increased Creatine level rather than decreased levels of NAA. This ratio which correlates well with motor functions does not normalize postoperatively. In addition, post-shunting metabolic changes detected by MRS include increased post-operative Glutamate in the thalamus, significant increase in total Choline concentration (tCho) in the FDWM and a possible decrease in Myo-inositol (MI) in the frontal deep white matter. These changes are most likely markers of a mixed process of breakdown and repair.
- Conclusion: Despite small number of articles, high variability of techniques used and small sample size of these studies, there is some evidence that MRS can have a role in assessing shunt responsiveness in patient swith NPH FDWM and the thalamus were examined both pre and post-shunting. The basal ganglia have not been analyzed by MRS to assess relevant metabolic changes. Following shunting NAA/Cr ratios decrease, increase in Glutamate, tCho and Myo-inositol are the key findings identified so far by the available literature. Future research picking up where those articles ended and taking into considerations all the technical difficulties encountered by them may lead to better understanding of the pathophysiology of NPH and other neurodegenerative disorders, and also of the repair process when such conditions are relieved by treatment, hence the inclusion of MRS in the guidelines used to diagnosis and management of Normal Pressure Hydrocephalus and other Neurodegenerative conditions.