Neurosarcoidosis as a rapidly progressive dementia associated with normal pressure hydrocephalus.

Neurosarcoidosis (NS) is a rare subtype of sarcoidosis with a poor prognosis and diverse clinical presentations that often poses a diagnostic and therapeutic challenge. We describe the case of a 53-year-old male with an initial diagnosis of lingual sarcoidosis, who subsequently developed ataxia and rapidly progressive cognitive impairment. A lumbar puncture revealed hypoglycorrhachia, hyperproteinorrachia, lymphocytic pleocytosis, and elevated IL-6 levels (600 pg/ml). Cerebrospinal fluid flow cytometry showed an elevated CD4 lymphocyte concentration and a CD4+/CD8+ ratio of 3.91, indicative of NS. Brain MRI showed hyperintense periventricular and subcortical lesions on FLAIR/T2 resembling progressive multifocal leukoencephalopathy (PML), although negative PCR for JC virus ruled out the differential diagnosis. Following a favorable evolutionary course with corticosteroid pulses, the patient relapsed with normotensive hydrocephalus, treated with immunosuppressants and ventriculoperitoneal shunting with a good response to date. This case underscores the importance of maintaining a high index of suspicion for NS in individuals with sarcoidosis and neurologic symptoms. In these cases, cerebrospinal fluid biomarkers such as IL-6 and CD4+/CD8+ ratio are essential to guide the diagnosis. Furthermore, it highlights that hydrocephalus is a rare complication and requires a multidisciplinary approach, including medical and neurosurgical treatment.

La neurosarcoidosis es un subtipo raro de sarcoidosis con mal pronóstico y diversas presentaciones clínicas que a menudo plantea un reto diagnóstico y terapéutico. Describimos el caso de un varón de 53 años con diagnóstico inicial de sarcoidosis lingual, que posteriormente desarrolló ataxia y deterioro cognitivo de rápida evolución. Una punción lumbar reveló hipoglucorraquia, hiperproteinorraquia, pleocitosis linfocítica y niveles elevados de IL-6 (600 pg/ml). La citometría de flujo del líquido cefalorraquídeo mostró una concentración elevada de linfocitos CD4 y un cociente CD4+/CD8+ de 3.91, indicativo de neurosarcoidosis. La RM cerebral evidenció lesiones hiperintensas periventriculares y subcorticales en FLAIR/T2 que se asemejaban a una leucoencefalopatía multifocal progresiva (LMP), aunque la PCR negativa para el virus JC descartó el diagnóstico diferencial. Tras un curso evolutivo favorable con pulsos de corticoides, el paciente recayó con hidrocefalia normotensiva, tratada con inmunosupresores y derivación ventriculoperitoneal con buena respuesta hasta la fecha. Este caso subraya la importancia de mantener un alto índice de sospecha de neurosarcoidosis en individuos con sarcoidosis y síntomas neurológicos. En estos casos, los biomarcadores del líquido cefalorraquídeo tales como la IL-6 y el cociente CD4+/CD8+ son esenciales para orientar el diagnóstico. Además, destaca que la hidrocefalia es una complicación poco frecuente y requiere un abordaje multidisciplinario, que incluya tratamiento médico y neuroquirúrgico.

Neurosarcoidosis as a rapidly progressive dementia associated with normal pressure hydrocephalus / Neurosarcoidosis como demencia rápidamente progresiva asociada a hidrocefalia normotensiva

Abstract Neurosarcoidosis (NS) is a rare subtype of sarcoidosis with a poor prognosis and diverse clinical presentations that often poses a diagnostic and therapeutic challenge. We describe the case of a 53-year-old male with an initial diagnosis of lingual sarcoidosis, who subsequently developed ataxia and rapidly progressive cognitive im pairment. A lumbar puncture revealed hypoglycorrha chia, hyperproteinorrachia, lymphocytic pleocytosis, and elevated IL-6 levels (600 pg/ml). Cerebrospinal fluid flow cytometry showed an elevated CD4 lymphocyte con centration and a CD4+/CD8+ ratio of 3.91, indicative of NS. Brain MRI showed hyperintense periventricular and subcortical lesions on FLAIR/T2 resembling progressive multifocal leukoencephalopathy (PML), although nega tive PCR for JC virus ruled out the differential diagnosis. Following a favorable evolutionary course with cortico steroid pulses, the patient relapsed with normotensive hydrocephalus, treated with immunosuppressants and ventriculoperitoneal shunting with a good response to date. This case underscores the importance of maintain ing a high index of suspicion for NS in individuals with sarcoidosis and neurologic symptoms. In these cases, ce rebrospinal fluid biomarkers such as IL-6 and CD4+/CD8+ ratio are essential to guide the diagnosis. Furthermore, it highlights that hydrocephalus is a rare complication and requires a multidisciplinary approach, including medical and neurosurgical treatment.

Resumen La neurosarcoidosis es un subtipo raro de sarcoidosis con mal pronóstico y diversas presentaciones clínicas que a menudo plantea un reto diagnóstico y terapéutico. Describimos el caso de un varón de 53 años con diagnóstico inicial de sarcoidosis lingual, que posterior mente desarrolló ataxia y deterioro cognitivo de rápida evolución. Una punción lumbar reveló hipoglucorraquia, hiperproteinorraquia, pleocitosis linfocítica y niveles elevados de IL-6 (600 pg/ml). La citometría de flujo del líquido cefalorraquídeo mostró una concentración ele vada de linfocitos CD4 y un cociente CD4+/CD8+ de 3.91, indicativo de neurosarcoidosis. La RM cerebral evidenció lesiones hiperintensas periventriculares y subcorticales en FLAIR/T2 que se asemejaban a una leucoencefalopa tía multifocal progresiva (LMP), aunque la PCR negativa para el virus JC descartó el diagnóstico diferencial. Tras un curso evolutivo favorable con pulsos de corticoides, el paciente recayó con hidrocefalia normotensiva, tratada con inmunosupresores y derivación ventriculoperitoneal con buena respuesta hasta la fecha. Este caso subraya la importancia de mantener un alto índice de sospecha de neurosarcoidosis en individuos con sarcoidosis y síntomas neurológicos. En estos casos, los biomarcadores del líquido cefalorraquídeo tales como la IL-6 y el cociente CD4+/CD8+ son esenciales para orientar el diagnóstico. Además, destaca que la hidro cefalia es una complicación poco frecuente y requiere un abordaje multidisciplinario, que incluya tratamiento médico y neuroquirúrgico.

Management of shunt dysfunction using noninvasive intracranial pressure waveform monitoring: illustrative case.

BACKGROUND: Normal pressure hydrocephalus (NPH) treatment consists of using valves for drainage, as it is for hydrocephalus in general. Despite this, complications can occur, putting the patient at risk, and neurological monitoring is crucial. OBSERVATIONS: A 61-year-old male, who had been diagnosed with NPH 3 years prior and was being treated with a ventriculoperitoneal shunt with a programmable valve, presented to the emergency department because of a traumatic brain injury due to a fall from standing height. No previous complications were reported. He had an altered intracranial pressure (ICP) waveform in the emergency room when monitored with the brain4care device, with a P2/P1 ratio of 1.6. Imaging helped to confirm shunt dysfunction. Revision surgery normalized the ratio to 1.0, and the patient was discharged. Upon return after 14 days, an outpatient analysis revealed a ratio of 0.6, indicating improvement. LESSONS: In selected cases of NPH, noninvasive ICP waveform morphology analysis can be effective as a diagnostic aid, as well as in the pre- and postsurgical follow-up, given the possibility of comparing the values of ICP preoperatively and immediately postoperatively and the outpatient P2/P1 ratio, helping to manage these patients.

Treatment of Idiopathic Normal Pressure Hydrocephalus with a Novel Programmable Valve: Prospective Evaluation of Costs, Efficacy, and Safety.

Objective Programmable valves provide an equal or superior neurological outcome when compared with fixed pressure ones, with fewer complications, in treating idiopathic normal pressure hydrocephalus (iNPH) patients. Long-term costs of these treatments have not been properly compared in literature. We sought to compare costs, efficacy, and safety of 1-year treatment of iNPH patients with programmable valve Sphera Pro and a fixed pressure valve. Materials and Methods A prospective cohort of iNPH patients treated with programmable valve was compared with a historical cohort of iNPH patients treated with fixed pressure valve. Our primary outcome was mean direct cost of treating iNPH up to 1 year. Efficacy in treating iNPH and safety were assessed as secondary outcomes. Statistical Analysis Proportions were compared using chi-square or Fisher's exact tests. Normally distributed variables were compared using the Student's t -test or the Mann-Whitney's U test. Differences in the evolution of the variables over time were assessed using generalized estimating equations. All tests were two-sided, with an α of 0.05. Results A total of 19 patients were analyzed in each group (mean age 75 years, the majority male). Comorbidities and clinical presentation were similar between groups. Both fixed pressure and programmable valve patients had neurological improvement over time ( p < 0.001), but no difference was seen between groups ( p = 0.104). The fixed pressure valve group had more complications than the programmable valve group (52.6% vs. 10.5%, respectively, p = 0.013). Annual treatment cost per patient was US$ 3,820 ± 2,231 in the fixed pressure valve group and US$ 3,108 ± 553 in the programmable valve group. Mean difference was US$712 (95% confidence interval, 393-1,805) in favor of the programmable valve group. Conclusion The Sphera Pro valve with gravitational unit had 1 year treatment cost not higher than that of fixed pressure valve, and resulted in similar efficacy and fewer complications.

Comparison of Noninvasive Measurements of Intracranial with Tap Test Results in Patients with Idiopathic Normal Pressure Hydrocephalus.

Background: Normal pressure hydrocephalus is a disease directly related to the change in intracranial compliance and consequent repercussions in the brain parenchyma. Invasive monitoring of such parameters proves to be reliable especially for prognosis in neurocritical patients; however, it is not applicable in an outpatient service setting. The present study describes the comparison between the tap test results and the parameters obtained with a non-invasive sensor for monitoring intracranial compliance in patients with suspected NPH. Methods: Twenty-eight patients were evaluated before and after lumbar puncture of 50mL of CSF (the tap test), comprising clinical assessment, magnetic resonance imaging, physical therapy assessment using the Timed Up and Go test, Dynamic Gait Index, BERG test, neuropsychological assessment, and recording of non-invasive intracranial compliance data using the Brain4care® device in three different positions (lying, sitting, and standing) for 5 min each. The tap test results were compared to the Time to Peak and P2/P1 ratio parameters obtained by the device. Results: The group that had a positive Tap test result presented a median P2/P1 ratio greater than 1.0, suggesting a change in intracranial compliance. In addition, there was also a significant difference between patients with positive, negative, and inconclusive results, especially in the lying position. Conclusion: A non-invasive intracranial compliance device when used with the patient lying down and standing up obtained parameters that suggest correspondence with the result of the tap test.

Normal pressure hydrocephalus decreases the proliferation of oligodendrocyte progenitor cells and the expression of CNPase and MOG proteins in the corpus callosum before behavioral deficits occur.

Normal pressure hydrocephalus (NPH) compromises the morphology of the corpus callosum (CC). This study aims to determine whether 60- or 120-day NPH disrupts the cytoarchitecture and functioning of white matter (WM) and oligodendrocyte precursor cells (OPCs) and establish whether these changes are reversible after hydrocephalus treatment. NPH was induced in CD1 adult mice by inserting an obstructive lamina in the atrium of the aqueduct of Sylvius. Five groups were assembled: sham-operated controls (60 and 120 days), NPH groups (60 and 120 days), and the hydrocephalus-treated group (obstruction removal after 60-d hydrocephalus). We analyzed the cellular integrity of the CC by immunohistochemistry, TUNEL analysis, Western blot assays, and transmission electron microscopy (TEM). We found a reduction in the width of the CC at 60 and 120 days of NPH. TEM analysis demonstrated myelin abnormalities, degenerative changes in the WM, and an increase in the number of hyperdense (dark) axons that were associated with significant astrogliosis, and microglial reactivity. Hydrocephalus also caused a decrease in the expression of myelin-related proteins (MOG and CNPase) and reduced proliferation and population of OPCs, resulting in fewer mature oligodendrocytes. Hydrocephalus resolution only recovers the OPC proliferation and MOG protein density, but the rest of the WM abnormalities persisted. Interestingly, all these cellular and molecular anomalies occur in the absence of behavioral changes. The results suggest that NPH severely disrupts the myelin integrity and affects the OPC turnover in the CC. Remarkably, most of these deleterious events persist after hydrocephalus treatment, which suggests that a late treatment conveys irreversible changes in the WM of CC.

Ten Steps for NPH Management: Advancements in Diagnosis and Treatment of Adult Hydrocephalus / Dez etapas para o manejo da NPH: avanços no diagnóstico e tratamento da hidrocefalia em adultos

Objectives The authors of the present study intend to describe a straightforward protocol for normal pressure hydrocephalus diagnosis and management, with the employment of a multidisciplinary team approach effort. Methods Using a strict methodological approach for initial diagnosis, taking into consideration occupational therapy and physical therapy assessment, the authors have set out to elaborate a simple protocol for suspicion and, once diagnosed, treatment of normal pressure hydrocephalus. We have used the MoCA (Montreal Cognitive Assessment) and walking assessment that included speed, independence, and distance (SID), 10 m walk test, TUG (timed up and go) evaluation, 6-minute Walk Test, MiniBESTest, as the main factors for pre and post lumbar drainage assessment, after which, the alternatives were deliberated and followed, or not, by ventriculoperitoneal shunt insertion. Results The authors have described a protocol, consisting of ten easy steps, which involves a multidisciplinary team, including occupational therapy and physical therapy professionals, as well as neurologists and neurosurgeons for improved and objective assessment prior to insertion of lumbar drain and, thereafter, detecting the population at most benefit for ventriculoperitoneal shunt insertion. We have described the Ten Step Approach for Normal Pressure Hydrocephalus management, including from initial clinical presentation and imaging, to pre and post lumbar drainage, for lastly deciding upon necessity for ventriculoperitoneal shunt insertion. Conclusions A straightforward protocol for normal pressure hydrocephalus seems not only feasible, but simple to implement in most neurosurgical departments, with good accuracy of prediction of lumbar drainage assessment to shunting outcomes.

Normal pressure hydrocephalus associated with COVID-19 infection: a case report.

BACKGROUND: COVID-19 is a pandemic disease responsible for many deaths worldwide. Many neurological manifestations have been described. We report a case of normal pressure hydrocephalus (NPH) 2 months after acute COVID19 infection, in a patient without other risk factors. CASE PRESENTATION: A 45-year-old male patient presented an 8-month history of progressive gait disorder and cognitive impairment after being hospitalized for SARS-CoV-2 infection. Magnetic resonance imaging (MRI) was compatible with NPH. A spinal tap test was positive and there was progressive improvement after shunting, with complete resolution of symptoms. CONCLUSION: Other infections such as syphilis, cryptococcosis and Lyme disease have been associated with NPH. Possible mechanisms for NPH after COVID include disruption of choroid plexus cells by direct viral invasion or as a result of neuroinflammation and cytokine release and hypercoagulability leading to venous congestion and abnormalities of CSF flow. Given the significance of NPH as a cause of reversible dementia, it is important to consider the possibility of a causal association with COVID19 and understand the mechanisms behind this association.

Ventriculo-atrial shunt. Comparison of an ultrasound-guided peel-away technique versus conventional technique in the management of normal pressure hydrocephalus: A retrospective cohort.

BACKGROUND: Normal pressure hydrocephalus (NPH) is a common neurodegenerative syndrome among the elderly characterized by ventriculomegaly and the classic triad of symmetric gait disturbance, cognitive decline and urinary incontinence. To date, the only effective treatment is a cerebrospinal fluid shunting procedure that can either be ventriculo-atrial, ventriculo-peritoneal, or lumbo-peritoneal shunt. The conventional ventriculo-atrial shunt uses venodissection, whereas the peel-away is a percutaneous ultrasound (US)-guided technique that shows some advantages over conventional technique. We sought to compare perioperative complication rates, mean operating time and clinical outcomes for both techniques in NPH patients at our institution. METHODS: A retrospective cohort-type analytical study was conducted, using clinical record data of patients diagnosed with NPH and treated at our center from January 2009 to September 2019. Parameters to be compared include: Perioperative complication rates, intraoperative bleeding, mortality, and mean operating time. Perioperative complication rates are those device-related such as shunt infection, dysfunction, and those associated with the procedure. Complications are further classified in immediate (occurring during the first inpatient stay), early (within the first 30 days of surgery), and late (after day 30 of surgery). RESULTS: A total of 123 patients underwent ventriculo-atrial shunt. Eighty-two patients (67%) underwent conventional venodissection technique and 41 patients (33%) underwent a peel-away technique. Immediate complications were 3 (3.6%) and 0 for conventional and peel-away groups, respectively. Early complications were 0 and 1 (2.4%) for conventional and peel-away groups, respectively. Late complications were 5 (6.1%) and 2 (4.9%) for conventional and peel-away groups, respectively. Mean operating time was lower in the peel-away group (P = 0.0000) and mortality was 0 for both groups. CONCLUSION: Ventriculo-atrial shunt is an effective procedure for patients with NPH. When comparing the conventional venodissection technique with a percutaneous US-guided peel-away technique, the latter offers advantages such as shorter operating time and lower perioperative complication rates.

Salomón Hakim, MD (1922-2011): A honeymoon with Neurosurgery.

Salomón Hakim (1922-2011) was a Colombian neurosurgeon and brain scientist This biography examines the social and cultural background through which he emerged as an inquisitive and multi-dimensional surgeon-scientist, and his lifelong contributions to the specialty of neurosurgery. With empirical knowledge in applied medical physics, electronics, electricity and chemistry, he understood the paradoxical phenomenon of symptomatic hydrocephalus with normal cerebrospinal fluid pressure. This ultimately led Hakim to describe in exquisite detail the physics of the cranial cavity and brain hydrodynamics. His name is intertwined with the identification of the entity of a syndrome which had not previously been addressed in the medical literature: Normal Pressure Hydrocephalus (Hakim's syndrome). Additionally, he designed and built various models of valved shunting devices to treat the condition (eg the Hakim programmable valve). Through his selflessness and cogent work, Hakim left a legacy and intellectual heritage that has allowed many colleagues worldwide to save thousands of lives who would be otherwise condemned to oblivion.

Characterization of a mouse model of chronic hydrocephalus induced by partial occlusion of the aqueduct of Sylvius in the adult brain.

BACKGROUND: Hydrocephalus is a neurologic disturbance produced by the abnormal production, circulation, and absorption of cerebrospinal fluid (CSF). Late-onset idiopathic aqueductal stenosis induces normal pressure hydrocephalus (NPH) in adults. To date, no animal model replicating chronic NPH is available to study the pathophysiological changes observed in these subjects. NEW METHOD: We performed and characterized a model that induces chronic hydrocephalus in the adult mouse brain by producing a pre-aqueductal semiobstruction using an acetate lamina inserted into the atrium of the aqueduct of Sylvius. After surgical procedure, we analyzed the hydrocephalus development on days 60 and 120 and sham-operated animals were used as controls. We included an additional group of hydrocephalus resolution in which we removed the obstruction and analyzed the morphological changes in the brain. RESULTS: The hydrocephalus was fully established on day 60 after the obstruction and remained stable for 120 days. In all animals, the intracranial pressure remained ~4.08 mmHg and we did not find statistically significant differences between the hydrocephalus groups and controls. We did not find motor impairments and anxiety-like behaviors among groups and the analysis of microglia and astrogliosis revealed mild glial reactivity. COMPARISON WITH EXISTING METHODS: This model generates a long-term ventricular enlargement with normal intracranial pressure and moderate glial reactivity. Importantly, this model allows the reversibility of ventricular enlargement after the removal of the obstructive film from the brain. CONCLUSIONS: This mouse model may be useful to study the long-term cerebral alterations that occur during NPH or after its surgical resolution.

Serial Tap Test of patients with idiopathic normal pressure hydrocephalus: impact on cognitive function and its meaning.

BACKGROUND: Idiopathic normal pressure hydrocephalus (INPH) is characterized by gait disturbance, urinary incontinence and cognitive decline. Symptoms are potentially reversible and treatment is based on cerebrospinal fluid shunting. The tap test (TT) is used to identify patients that will benefit from surgery. This procedure consists of the withdrawal of 20 to 50 mL of cerebrospinal fluid (CSF) through a lumbar puncture (LP) after which the symptoms of the triad are tested. Improvement in the quality and speed of gait are already recognized but cognitive improvement depends on several factors such as tests used, the time elapsed after LP for re-testing, and the number of punctures. Serial punctures may trigger similar conditions as external lumbar drainage (ELD) to the organism. OBJECTIVE: This study aimed to identify how serial punctures affect cognition to increase the sensitivity of the test and consequently the accuracy of surgical indication. METHODS: Sixty-one patients with INPH underwent baseline memory and executive tests repeatedly following the 2-Step Tap Test protocol (2-STT - two procedures of 30 mL lumbar CSF drainage separated by a 24-h interval). The baseline scores of INPH patients were compared with those of 55 healthy controls, and with intragroup post-puncture scores of the 2-STT. RESULTS: The group with INPH had lower performance than the control group in all cognitive tests (RAVLT, Stroop, CFT, FAR-COWA, FAB, MMSE, orientation, mental control), except for the forward digit span test (p = 0.707). After conducting LP procedures, the Stroop test (words, colors and errors), RAVLT (stage A1, A6 and B1), and CFT (immediate and delayed R) scores were equal to those of the control group (p > 0.05). The INPH group presented significant improvement after the first puncture in MMSE (p = 0.031) and in the Stroop Test (points) (p < 0.001). After the second puncture, subjects improved in orientation, MMSE, RAVLT (B1), Stroop (points, words, errors) and CFT (IR). CONCLUSION: Progressive cognitive improvement occurred over the 2-STT and changes were more significant after the second LP in all cognitive domains except for RAVLT (A7). Encephalic alert system 'arousal' seems to participate in early improvements observed during 2-STT. The second LP increased the sensitivity of the drainage test to detect changes in cognitive variables, and consequently improved the quality of the method.

Long term follow-up of shunted idiopathic normal pressure hydrocephalus patients: a single center experience.

Idiopathic normal pressure hydrocephalus (iNPH) is a condition characterized by gait disturbance, dementia and/or urinary incontinence and enlarged ventricular system due to disturbance of cerebrospinal fluid (CSF). This study aims to describe the long-term experience with patients with iNPH submitted to ventriculoperitoneal shunt (VPS) with the programmable valve STRATA® (Medtronic). We prospectively selected a cohort of patients with a diagnosis of iNPH from January 2010 to April 2013 in a Brazilian tertiary hospital. All patients underwent clinical evaluation, which consists of the Mini-Mental State Examination and Time Up and Go tests and the application of Japanese Scale for Idiopathic Normal Pressure Hydrocephalus in three stages: prior to the TT, 3 h after the TT and 72 h after the TT. Fifty patients were submitted to VPS and followed. There were 32 men and 18 women. Mean age was 77.1 with standard deviation of 10.9. Follow-up time ranged from 96 to 120 months, with mean of 106 months. After 1 year of follow-up, 42 (83%) patients presented with clinical improvement, decreasing to 62% of patients at mid-term follow-up and 38% of patients at late follow-up. Complications occurred in 18% of subjects, needing reoperation in 16%. Our results show relevant clinical impact of shunting in iNPH patients, decreasing over time. Complications should not be underestimated, reaching up to 18% and demanding reoperation in 16% of cases. Thus, although much has been improved with current shunt technology, it is still important to consider the drawbacks of treatment.

Predictors of favorable response to implanted of ventriculoperitoneal shunt in patients with idiopathic normal pressure hydrocephalus / Predictores de respuesta favorable a la colocación de derivación ventriculoperitoneal en pacientes con hidrocefalia normotensiva idiopática

Introduction: The indication of a ventriculoperitoneal shunt (VPS) is discussed in patients with idiopathic normal pressure hydrocephalus (iNPH), due to the heterogeneity of the response to treatment and the risks involved in neurosurgery. Objective: To search for clinical factors and complementary studies in order to determine predictors of a favorable response to the VPS placement in patients with iNPH. Methodology: A retrospective study of patients with probable iNPH (according to international guidelines) treated with VPS assisted in a neurological clinic from January 2014 to January 2017 was conducted. A univariate statistical analysis of the variables considered as possible prognostic factors was performed. Results: 58 patients were included. Women presented 3.68 times more chances of improvement after the VPS (p=0.019). Good response to the gait test was associated with better response to the VPS (p=0.024). Conclusions: Female sex and good response to the gait test could be considered as predictors of a favorable response to the VPS placement in patients with iNPH. A prospective study is necessary to achieve a homogeneous diagnostic evaluation and a more extensive longitudinal follow-up to evaluate the clinical evolution in this group of patients.

Introducción: La indicación de la derivación ventriculoperitoneal (DVP) se discute en pacientes con hidrocefalia normotensiva idiopática (HNTi), debido a la hetero-geneidad de la respuesta al tratamiento y los riesgos que conlleva la neurocirugía. Objetivo: Búsqueda de factores clínicos y estudios complementarios, para deter-minar predictores de respuesta favorable a la colocación de DVP en pacientes con HNTi. Metodología: Estudio retrospectivo de pacientes con probable HNTi (según guías internacionales) tratados con DVP asistidos en una clnica neurológica desde enero de 2014 hasta enero de 2017. Se realizó un análisis estadístico univariado de las variables consideradas como posibles factores pronósticos. Resultados: se incluyeron 58 pacientes. Las mujeres presentaron 3,68 veces más posibilidades de mejora tras la DVP (p=0,019). La buena respuesta a la prueba de la marcha se asoció con una mejor respuesta a la DVP (p=0,024). Conclusiones: el sexo femenino y la buena respuesta a la prueba de la marcha podrían considerarse predictores de una respuesta favorable a la colocación de la DVP en pacientes con HNTi. Es necesario un estudio prospectivo para lograr una evaluación diagnóstica homogénea y un seguimiento longitudinal más extenso para evaluar la evolución clínica en este grupo de pacientes.

Cerebrospinal fluid closing pressure-guided tap test for the diagnosis of idiopathic normal pressure hydrocephalus: A descriptive cross-sectional study.

BACKGROUND: Tap test improves symptoms of idiopathic normal pressure hydrocephalus (iNPH); hence, it is widely used as a diagnostic procedure. However, it has a low sensitivity and there is no consensus on the parameters that should be used nor the volume to be extracted. We propose draining cerebrospinal fluid (CSF) during tap test until a closing pressure of 0 cm H2O is reached as a standard practice. We use this method with all our patients at our clinic. METHODS: This is a descriptive cross-sectional study where all patients with presumptive diagnosis of iNPH from January 2014 to December 2019 were included in the study. We used a univariate descriptive analysis and stratified analysis to compare the opening pressure and the volume of CSF extracted during the lumbar puncture, between patients in whom a diagnosis of iNPH was confirmed and those in which it was discarded. RESULTS: A total of 92 patients were included in the study. The mean age at the time of presentation was 79.4 years and 63 patients were male. The diagnosis of iNPH was confirmed in 73.9% patients. The mean opening pressure was 14.4 cm H2O mean volume of CSF extracted was 43.4 mL. CONCLUSION: CSF extraction guided by a closing pressure of 0 cm H2O instead of tap test with a fixed volume of CSF alone may be an effective method of optimizing iNPH symptomatic improvement and diagnosis.

Normal-pressure hydrocephalus: A critical review.

Normal-pressure hydrocephalus (NPH) is a potentially reversible syndrome characterized by enlarged cerebral ventricles (ventriculomegaly), cognitive impairment, gait apraxia and urinary incontinence. A critical review of the concept, pathophysiology, diagnosis, and treatment of both idiopathic and secondary NPH was conducted. We searched Medline and PubMed databases from January 2012 to December 2018 using the keywords "normal-pressure hydrocephalus" / "idiopathic normal-pressure hydrocephalus" / "secondary normal-pressure hydrocephalus" / "NPH" / "ventriculoperitoneal shunt". The initial search produced 341 hits. After careful selection, a total of 54 articles were chosen and additional relevant studies were included during the process of writing this article. NPH is an important cause of potentially reversible dementia, frequent falls and recurrent urinary infections in the elderly. The clinical and imaging features of NPH may be incomplete or nonspecific, posing a diagnostic challenge for medical doctors and often requiring expert assessment to minimize unsuccessful surgical treatments. Recent advances resulting from the use of non-invasive MRI methods for quantifying cerebral blood flow, in particular arterial spin-labeling (ASL), and the frequent association of NPH and obstructive sleep apnea (OSA), offer new avenues to understand and treat NPH.

A hidrocefalia de pressão normal (HPN) é uma síndrome potencialmente reversível marcada por ventrículos cerebrais alargados (ventriculomegalia), declínio cognitivo, apraxia da marcha e incontinência urinária. Revisar criticamente o conceito, a fisiopatologia, o diagnóstico e o tratamento da HPN idiopática e secundária. Os autores acessaram as bases de dados Medline e Pubmed entre janeiro de 2012 e dezembro de 2018, utilizando as palavras-chave "normal-pressure hydrocephalus" / "idiopathic normal-pressure hydrocephalus" / "secondary normal-pressure hydrocephalus" / "NPH" / "ventriculoperitoneal shunt". A busca inicial resultou em 341 artigos. Após cuidadosa seleção, 54 estudos foram escolhidos e pesquisas adicionais foram incluídas durante o processo de elaboração do manuscrito. A HPN é uma importante causa de demência potencialmente reversível, quedas frequentes e infecção urinária recorrente em idosos. As características clínicas e de imagem da HPN podem ser incompletas ou inespecíficas, de modo que este se torna um diagnóstico difícil para médicos. Não raro uma avaliação por especialista é necessária, visando minimizar tratamentos cirúrgicos ineficazes. Avanços recentes advindos do uso não invasivo de ressonância magnética para quantificação do fluxo sanguíneo cerebral, em particular arterial spin-labeling (ASL), assim como a usual associação entre HPN e apneia obstrutiva do sono representam novos meios de entender e de tratar a HPN.

Normal-pressure hydrocephalus: A critical review / Hidrocefalia de pressão normal: uma revisão crítica

ABSTRACT. Normal-pressure hydrocephalus (NPH) is a potentially reversible syndrome characterized by enlarged cerebral ventricles (ventriculomegaly), cognitive impairment, gait apraxia and urinary incontinence. A critical review of the concept, pathophysiology, diagnosis, and treatment of both idiopathic and secondary NPH was conducted. We searched Medline and PubMed databases from January 2012 to December 2018 using the keywords "normal-pressure hydrocephalus" / "idiopathic normal-pressure hydrocephalus" / "secondary normal-pressure hydrocephalus" / "NPH" / "ventriculoperitoneal shunt". The initial search produced 341 hits. After careful selection, a total of 54 articles were chosen and additional relevant studies were included during the process of writing this article. NPH is an important cause of potentially reversible dementia, frequent falls and recurrent urinary infections in the elderly. The clinical and imaging features of NPH may be incomplete or nonspecific, posing a diagnostic challenge for medical doctors and often requiring expert assessment to minimize unsuccessful surgical treatments. Recent advances resulting from the use of non-invasive MRI methods for quantifying cerebral blood flow, in particular arterial spin-labeling (ASL), and the frequent association of NPH and obstructive sleep apnea (OSA), offer new avenues to understand and treat NPH.

RESUMO. A hidrocefalia de pressão normal (HPN) é uma síndrome potencialmente reversível marcada por ventrículos cerebrais alargados (ventriculomegalia), declínio cognitivo, apraxia da marcha e incontinência urinária. Revisar criticamente o conceito, a fisiopatologia, o diagnóstico e o tratamento da HPN idiopática e secundária. Os autores acessaram as bases de dados Medline e Pubmed entre janeiro de 2012 e dezembro de 2018, utilizando as palavras-chave "normal-pressure hydrocephalus" / "idiopathic normal-pressure hydrocephalus" / "secondary normal-pressure hydrocephalus" / "NPH" / "ventriculoperitoneal shunt". A busca inicial resultou em 341 artigos. Após cuidadosa seleção, 54 estudos foram escolhidos e pesquisas adicionais foram incluídas durante o processo de elaboração do manuscrito. A HPN é uma importante causa de demência potencialmente reversível, quedas frequentes e infecção urinária recorrente em idosos. As características clínicas e de imagem da HPN podem ser incompletas ou inespecíficas, de modo que este se torna um diagnóstico difícil para médicos. Não raro uma avaliação por especialista é necessária, visando minimizar tratamentos cirúrgicos ineficazes. Avanços recentes advindos do uso não invasivo de ressonância magnética para quantificação do fluxo sanguíneo cerebral, em particular arterial spin-labeling (ASL), assim como a usual associação entre HPN e apneia obstrutiva do sono representam novos meios de entender e de tratar a HPN.

Deep Brain Stimulation Surgery for Parkinson Disease Coexisting With Communicating Hydrocephalus: A Case Report.

We report a successful bilateral globus pallidus internus-deep brain stimulation (GPi-DBS) for a Parkinson disease (PD) patient with idiopathic normal pressure hydrocephalus (INPH) and an unusually long anterior commissure-posterior commissure (AC-PC) line. A 54-year-old man presented with a history of 3 months of severe shuffling gait, rigidity, slow movements of the left side limbs, and difficulty managing finances. A brain MRI revealed marked ventriculomegaly (Evans index = 0.42). The patient was diagnosed with INPH and a ventriculoperitoneal shunt was placed. Cognitive impairment improved, but walking disturbances, slowness, and rigidity persisted. Then treatment with levodopa was added, and the patient experienced a sustained improvement. He was diagnosed with PD. After 7 years, the patient developed gait freezing and severe levodopa-induced dyskinesia. The patient underwent bilateral GPi-DBS. We used MRI/CT fusion techniques for anatomical indirect targeting. Indirect targeting is based on standardized stereotactic atlas and on a formula-derived method based on AC-PC landmarks. The AC-PC line was 40 mm (the usual length is between 19 and 32 mm). Intraoperative microelectrode recording was a non-expendable test, but multiple recordings were avoided to reduce the surgical risk of ventricular involvement. There was a 71% decrease in the UPDRS III score during the on-stimulation state (28 to 8). The patient's dyskinesias resolved dramatically with a UdysRS of 15 (88% improvement) during the on-stimulation condition. The observed motor benefits and the improvement of his daily activities have persisted 6 months after surgery. Deep brain stimulation surgery in PD with ventriculomegaly is a challenge. This procedure can result in a greater chance of breaching the ventricle, with risks of intraventricular hemorrhage and migration of cerebrospinal fluid into the brain parenchyma with target displacement. Furthermore, clinical judgment is paramount when recent onset of shuffling gait coexists with ventriculomegaly because the most common dilemma is differentiating between PD and INPH. For these reasons, neurologists and surgeons may refuse to operate on PD patients with ventriculomegaly. However, DBS should be considered for PD patients with motor complications when responsiveness to levodopa is demonstrated, even in the context of marked ventriculomegaly.

Ventricular Volume Dynamics During the Development of Adult Chronic Communicating Hydrocephalus in a Rodent Model.

INTRODUCTION: The pathophysiology of normal-pressure hydrocephalus and the correlation with its symptomatology is not well understood. OBJECTIVE: To monitor and evaluate the enlargement patterns of the ventricular system for each ventricle and its correlation with the presenting symptoms. METHODS: Bilateral kaolin injection into the subarachnoid space overlying the cranial convexities was done in 18 adult rats. Magnetic resonance imaging was performed on an 11.7-T scanner 15, 60, 90, and 120 days after injection. Volumes of the ventricular system were measured for each ventricle and correlated with biweekly behavioral findings. RESULTS: There was a progressive increase in the ventricular volume for the lateral ventricles since day 15 in the kaolin-injected animals. There was a nonsignificant trend in volume growth for the third ventricle, but its enlargement was synchronous with the lateral ventricles. No significant change for the fourth ventricle. No symptoms were detected in the first 60 days. Association was found between the ventricular volume and locomotor changes. In addition, the odds of locomotor symptoms increased by 3% for every additional cubic millimeter of volume in the left (P < 0.001) and right (P = 0.023) ventricles, and for the total magnetic resonance imaging volume by 1% (P = 0.013). CONCLUSIONS: Expansion of the lateral ventricles maintained similar proportions over time, accompanied by a synchronous third ventricular expansion with less proportion and a nonsignificant fourth enlargement. Lateral ventricles enlarged most in those animals that were to develop late locomotor deterioration. Further research using this animal model combined with different radiologic imaging techniques, such as diffusion tensor imaging and perfusion studies, is recommended.

Síndrome Neuropsicológico Frontal como Consecuencia de Hidrocefalia de Tensión Normal: estudio de caso / Frontal Neuropsychological Syndrome as a Consequence of Normal Tension Hydrocephalus: a case study

Resumen La manifestación clínica de la Hidrocefalia de Tensión Normal (NPH) implica pérdida del control de esfínter vesical, trastorno de la marcha y deterioro cognitivo. Este estudio buscó describir el estado neuropsicológico funcional de una paciente con NPH a través del análisis sindrómico, aplicando pruebas neuropsicológicas cualitativas y la evaluación de la actividad intelectual. Se evidenciaron dificultades y errores característicos del síndrome frontal severo con predominio de dificultades severas en la regulación y control de la actividad. Se observaron errores sistemáticos derivados de una falta de planeación, de selectividad y de autocrítica, en tareas perceptivas, verbales e intelectuales complejas. En el caso observado, el análisis neuropsicológico cualitativo apoya la afirmación de atrofia cortical con predominio frontal en esta enfermedad.

Abstract The clinical manifestation of Normal Pressure Hydrocephalus (NPH) implies loss of bladder sphincter control, gait disorder and cognitive impairment. The aim of this study is to describe the NPH patient's functional neuropsychological state through a syndromic analysis, applying qualitative neuropsychological tests and assessment of intellectual activity. It is evidenced difficulties and errors, which characterize severe syndrome with self-regulation and control of the activity. In the case of NPH, such syndrome is a consequence of organic frontal damage. Systematic errors derived from a lack of planning, selectivity and self-criticism were observed in complex perceptual, verbal and intellectual tasks. In this case, the qualitative neuropsychological analysis supports the affirmation of a cortical atrophy with frontal predominance in NPH.