A Retrospective Comparison of Long-Term Treatment Results of Subcutaneous Stimulation and Spinal Cord Stimulation for Chronic Neuralgia.

OBJECTIVES: Spinal cord stimulation (SCS) is known to be an effective long-term treatment option for chronic neuropathic pain. Subcutaneous stimulation (SubQ) is increasingly used to treat chronic back and neck pain, but long-term outcomes are unclear. MATERIALS AND METHODS: Patients with neurostimulation devices implanted during the past 16 years were evaluated. Their continuation or termination of the treatment was taken as a measure of long-term treatment success. Age, sex, underlying pain condition, stimulation modality (SCS, SubQ, or hybrid), occurrence, and reasons for treatment termination were documented. Patients were classified as long-term responders and long-term nonresponders and analyzed with their clinical data and stimulation modality. The sample consisted of 98 patients. Of these, 66 were treated with SCS, 21 with SubQ, and 11 with a hybrid system. RESULTS: Approximately 61.3% of patients receiving SubQ terminated the treatment within two years because of ineffectiveness, whereas only 28.8% of patients receiving SCS terminated their stimulation. Back and neck pain were associated with treatment termination (p = 0.011). SubQ was also significantly associated with treatment termination. CONCLUSIONS: SubQ seems not to provide substantial long-term pain relief for back and neck pain because most patients abandoned their stimulation therapy.

CSF shunt valve occlusion-does CSF protein and cell count matter?

BACKGROUND: Shunt obstruction is a common cause of shunt failure in the treatment of hydrocephalus. Valve occlusion is traditionally believed to originate from elevated CSF protein or cellular components, although detailed evidence is scarce and contradictory. Therefore, this study aimed to examine CSF protein and cell count as risk factors for valve obstruction. METHODS: We retrospectively examined 274 patients who underwent shunt placement for hydrocephalus between 2009 and 2018 and had at least 1 year follow-up. Age, aetiology of hydrocephalus, valve type, occurrence of revision, reason for revision and CSF protein and cell count at the time of shunt insertion and revision surgery were analysed. RESULTS: Thirty-two of 274 patients (11.7%) required revision surgery due to valve occlusion. Mean time to revision was 143 days. CSF white blood cell (WBC) count but not protein was associated with valve occlusion overall. Of all obstructed valve patients, 25% showed CSF protein level within the normal range, whereas 13.6% of the patients overall showed greatly elevated CSF protein level without evidence of valve obstruction. Persistently elevated CSF protein level at the time of shunt revision was significantly associated with valve obstruction within 90 days of initial insertion (early occlusion). Children with congenital malformations and post-haemorrhagic patients were significantly overrepresented in the occlusion group, particularly in the early occlusion group. CONCLUSION: Pathological CSF values such as WBC count and persistently elevated protein level serves as a risk factor for early valve obstruction. Late obstruction occurs independent of normal CSF values. Infants are particularly prone to early and late valve obstructions. CSF protein level at shunt insertion is not predictive of valve occlusion.

Treatment for secondary deterioration in idiopathic normal pressure hydrocephalus in the later course of the disease: a retrospective analysis.

BACKGROUND: Cerebrospinal fluid (CSF) shunting is a highly effective treatment for idiopathic normal pressure hydrocephalus (iNPH). However, secondary deterioration can occur at a later time. Thus, the current study aimed to evaluate the incidence rate and causes of secondary deterioration. METHODS: A retrospective analysis was conducted on all patients with iNPH who were treated with implantation of a CSF shunt since 1993. A meticulous shunt workup was recommended to all patients who presented to our department with secondary deterioration during their follow-up visits. Data about the proportion of patients with such deterioration and its causes, subsequent treatment, and clinical outcome were obtained. RESULTS: A total of 169 patients were included, and the mean follow-up time was 69.2 months. In total, 119 (70.4%) patients presented with a total of 153 secondary deteriorations. In 9 cases (5.9%), the deterioration was caused by delayed subdural hematoma and in 27 (22.1%) cases, by shunt dysfunction. Invasive shunt testing was commonly required to validate shunt failure. Moreover, 19 of 27 patients experienced a satisfactory improvement after revision surgery. In total, 86 deteriorations were attributed to nonsurgical causes, and the valve pressure was decreased in 79 patients, with only 16.5% presenting with a satisfactory improvement after lowering of valve pressure. CONCLUSIONS: Most patients with shunted iNPH presented with deterioration in the later course of the disease. Shunt dysfunction was considered a cause of secondary deterioration. Moreover, shunt revision surgery was a highly effective treatment, and patients with deterioration should undergo screening procedures for shunt dysfunction, including invasive shunt testing.

Ventriculoperitoneal Shunt Infections Cause Acute Abdomen and Peritonitis: A Case Series.

BACKGROUND: Patients with ventriculoperitoneal shunt (VPS) often present to emergency departments with acute abdomen. It is challenging to distinguish between the abdominal problems caused by a VPS and acute surgical abdomen having another cause because VPS infections occasionally cause peritonitis. The frequencies and clinical features of acute abdomen caused by VPS infection are unknown. METHODS: This was a retrospective analysis of all patients with a VPS who presented with acute abdomen to emergency department for a 10-year period. Clinical data, diagnostic workflow, and subsequent treatment were assessed using patient medical records. RESULTS: In total, 1679 patients presented with acute abdomen; of these, 24 (1.4%) had a VPS at the time of presentation. Of the 24 patients, 12 had an acute surgical abdomen related to gastrointestinal sources with subsequent therapy. In the remaining 12 patients (50%), peritonitis was caused by a VPS infection; seven of these had erroneous abdominal surgeries because of misdiagnosis. Patients with shunt infections as a source of peritonitis underwent shunt surgeries within the past 10 wk (mean, 58 d). Patients with an acute surgical abdomen with gastrointestinal sources had their most recent shunt surgery at a mean of 4.7 y before presentation to the emergency department. CONCLUSIONS: Acute abdomen and peritonitis are challenging in the presence of a VPS. Shunt infections frequently mimic acute surgical abdomen and may lead to misdiagnosis, unnecessary diagnostic procedures, unnecessary surgery, and delay in receiving the appropriate treatment. Shunt surgery in recent patient history is suggestive of VPS infection, and a shunt tap should be performed to confirm the diagnosis.

Revision surgery following CSF shunt insertion: how often could it be avoided?

BACKGROUND: Cerebrospinal fluid (CSF) shunt revision surgery represents a huge social and economic burden. Few studies, however, have evaluated shunt revision surgeries in the context of their avoidability, and existing data are from paediatric populations. Using ratings from an expert panel, we classified avoidable and unavoidable shunt revisions in a mixed cohort of CSF-shunt patients. METHODS: In a retrospective review of a prospectively maintained, single-centre database, we identified all shunt systems implanted for the first time over a 10-year period (2007-2016) and all subsequent revision surgeries with a follow-up of at least 1 year. A panel of five expert shunt surgeons classified each revision surgery as avoidable or unavoidable. Rates of each were calculated and correlated with clinical data. RESULTS: Of 210 revision surgeries (314 patients, mean age, 49.9 years; mean follow-up, 4.2 years), the panel judged 114 as unavoidable (54.3%) and 96 (45.7%) as avoidable. Level of surgeon education correlated with these rates, but even in the most experienced hands, 12.5% of revisions were classified as avoidable. Avoidable revisions occurred significantly earlier than unavoidable interventions (mean; 112 and 448 days, respectively) after the index surgery. CONCLUSION: Rates of avoidable shunt revision surgery are alarmingly high, even in experienced hands. Avoidable revisions occur significantly earlier, predominantly within the first 3 months after the index surgery.

Conservative versus operative treatment in supratentorial intracerebral hemorrhage - A survey among neurosurgeons and neurologists in Germany.

OBJECTIVES: Decision making for surgical therapy in patients with intracerebral hemorrhage is still controversial among neurologists and neurosurgeons. Whereas neurologists may favor conservative treatments, surgeons may opt for operations. This might lead to different therapy decisions. PATIENTS AND METHODS: Between 2017 and 2018, we conducted a survey among the neurological and neurosurgical societies in Germany. An online questionnaire consisting of 10 fictive patients with spontaneous supratentorial intracerebral hemorrhage (including CT scans and brief case descriptions) was administered to the members of the societies. The participants were asked to decide whether conservative or surgical treatment would be preferred. Furthermore, the results from the neurosurgeons were compared to the results of our previous surveys in 1999 and 2009. RESULTS: A total of 157 answers were collected (response rate of 16.2%). Nineteen had to be excluded, leaving 138 for analysis (84 neurosurgeons and 54 neurologists). There were no significant differences in therapy decisions between neurologists and neurosurgeons in all ten cases. Comparing the answers from neurosurgeons with our previous results, there were no significant differences between the results from 1999, 2009 and 2017. CONCLUSIONS: Against common prejudices, the process of decision making for or against surgery in patients with spontaneous intracerebral hemorrhage is comparable among conservative physicians (neurologists) and neurosurgeons in Germany. This might be the result of joint efforts in spontaneous intracerebral hemorrhage (ICH) therapy, such as joint guidelines or a society of neurointensive care medicine.

Frequency of and Risk Factors for Chronification in Traumatic Acute Subdural Hematoma following Conservative Therapy.

BACKGROUND: In an aging society, traumatic head injuries, such as acute subdural hematomas (aSDHs), are increasingly common because the elderly are prone to falls and are often undergoing anticoagulation treatment. Especially in advanced age, cranial surgery such as craniotomies may put patients in further jeopardy. But if treatment is conservative, a chronic subdural hematoma (cSDH) may develop, requiring surgical evacuation. Existing studies have reported a correlation between several risk factors contributing to the frequency of chronification. To improve the prediction of the course of disease and to aid counseling patients and relatives, this study aimed to determine the frequency and the main risk factors influencing the process of chronification of an aSDH following conservative treatment. METHODS: We identified patients presenting between January 2012 and September 2017 at our neurosurgical department with an aSDH. All patients treated conservatively were selected retrospectively, and the following parameters were documented: age, sex, chronification status, Glasgow Coma Scale score on admission and discharge, hematoma thickness and density, the degree of midline shift (MLS), prior anticoagulants and administration of procoagulants, thrombosis management, other coagulopathies, initial length of hospital stay, interval between discharge and readmission, and interval between initial injury and date of surgery and last follow-up. The cohort was divided into patients with complete resolution of their aSDH, and patients who needed surgery due to chronification. RESULTS: A total of 75 conservatively treated patients with aSDH were included. A chronification was observed in 24 cases (32%). The process of chronification takes an average of 18 days (range: 10-98 days). The following factors were significantly associated with the process of chronification: age (p = 0.001), anticoagulant medication (acetylsalicylic acid [ASA], Coumadin, and novel anticoagulants [NOACs]) before injury (p = 0.026), administration of procoagulants (p = 0.001), presence of other coagulopathies such as thrombocytopenia (p = 0.002), low hematoma density at discharge (p = 0.001), hematoma thickness on admission and discharge (p = 0.001), and the degree of MLS (p = 0.044). CONCLUSION: Chronification occurred in a third of all patients with conservatively treated aSDH, on average within 3 weeks. The probability of developing a cSDH is 0.96 times higher with every yearly increase in age, resulting in 56% chronification in patients ≥ 70 years. Hematoma thickness and impairment of the coagulation system such as anticoagulant medication (ASA, Coumadin, and NOACs) or thrombocytopenia are further risk factors for chronification.

Progress of intracranial pressure and cerebral perfusion pressure in patients during the development of brain death.

BACKGROUND: Clinical investigations of brain death are supposed to prove absence of cerebral perfusion. However, only limited data are available documenting intracranial pressure (ICP) and cerebral perfusion pressure (CPP) during the development of brain death. Our study presents additional data to understand the course of ICP and CPP in patients developing brain death. MATERIAL AND METHODS: We analyzed retrospective data of 18 patients with ICP monitoring during the development of brain death due to primary brain lesions. ICP and CPP values were continuously measured between two clinically defined time points: 1. non-reactive and widened pupils, 2. brain death determination. We analyzed ICP and CPP at the above-mentioned end points. Additionally, we investigated maximum ICP and minimal CPP values between these time points. RESULTS: Patients developed fixed and dilated pupils with a median of 38 h before brain death determination. During brain death determination median ICP and median CPP were 103.5 and -2.5 mmHg, respectively. Maximum ICP before brain death determination was significantly higher and minimal CPP values were significantly lower compared to the time point of brain death. During the investigation period all patients experienced ICP values >95 mmHg and CPP < 10 mmHg. All but one patient had documented CPP values of ≤0 mmHg. This single patient had a minimum CPP of 8 mmHg with a maximum ICP of 145 mmHg. CONCLUSION: Cerebral perfusion pressure during brain death determination may be positive in some patients. Our results showed variable values of ICP and CPP. However, extremely elevated ICP values before or during brain death in combination with low CPP values suggest absence of cerebral perfusion. The occurrence of positive CPP values during brain death determination therefore depends on the time point at which brain death determination is performed.

I can hear my shunt-audible noises associated with CSF shunts in hydrocephalic patients.

BACKGROUND: Cerebrospinal fluid (CSF) shunts are life-long implants, and patients have reported anecdotally on noises associated with their shunts. There is, however, a marked lack of information regarding acoustic phenomena related to CSF shunts. METHODS: We identified all patients who had been treated or followed in our neurosurgical department within a 15-year period from January 2000 up to the end of 2014. After approval of the local ethics committee all patients who were cognitively intact were explored by a questionnaire and by personal interview about acoustic phenomena related to their shunts. RESULTS: Three hundred forty-seven patients were eligible for the survey, and 260 patients completed the questionnaire. Twenty-nine patients (11.2%) reported on noises raised by their shunts. All of them experienced short-lasting noises while changing body posture, mainly from a horizontal to an upright position, or while reclining the head. Most of the patients reported on soft sounds, but loud and even very loud noises occurred in some patients. Seventy-six percent of the patients were not bothered by these noises as they considered it as a normal part of the therapy or as proof that the shunt device was functioning. Modern valves with gravitational units are prone to produce noises in young adults, but nearly all valve types can evoke noises. CONCLUSIONS: Noises caused by a shunt do occur in a considerable number of patients with shunts. One should be aware of this phenomenon, and these patients must be taken seriously.

Different origins of hydrocephalus lead to different shunt revision rates.

INTRODUCTION: Hydrocephalus (HC) occurs due to multiple origins. Time course and dynamic of HC and its therapies differ between underlying pathologies. Different revision rates due to the type of HC are expected. Though hydrocephalus is known to be a life time condition, the lack of shunt malfunction years or decades after initial shunt insertion raises the hope of a superfluous shunt. METHODS: We conducted a retrospective survey of our OR-database during a 10 year period. All newly inserted shunt systems and subsequent shunt revisions are recorded according to quantity and time point. All patients were subdivided according their aetiology of HC. RESULTS: 260 patients were eligible with a follow-up of 4.5 years. Subgroups were: 90 patients with NPH, 76 patients with posthaemorrhagic and 16 patients had posttraumatic HC. 22 received a shunt as a consequence of a tumour, 41 were children and 15 for other causes. Overall revision rate was 39.5%. During the first 6 months 55.6%, 57.9% and 75% of patients with NPH, posthaemorrhagic and posttraumatic HC had revisions. In contrast only 38.1% of children and 20% of tumour cases required early revision. CONCLUSION: Two different patterns of revision are evident: mainly early revisions in morphologically stable diseases such as posthaemorrhagic, posttraumatic and NPH and predominantly late revisions in changing organisms such as children and tumour patients. The conception HC may be transient because of a lack of late revisions cannot be supported by this data.

Early Physiotherapy by Passive Range of Motion Does Not Affect Partial Brain Tissue Oxygenation in Neurocritical Care Patients.

Background Studies investigating multimodal cerebral monitoring including partial brain tissue oxygen monitoring (ptiO2) in neuro-intensive care patients during physiotherapy are completely lacking in the literature. Materials and Methods We performed a post hoc analysis of prospectively collected data of patients on multimodal cerebral monitoring by intracranial pressure (ICP) and cerebral perfusion pressure (CPP) measurement as well as ptiO2. Patients with severe brain diseases were treated with passive range of motion (PROM). We recorded ICP, CPP, and ptiO2 continuously every minute at baseline (15 minutes), during treatment (26 minutes), and 15 minutes after treatment with PROM. Results Overall, 25 treatment units with PROM in 10 patients with combined ICP/CPP and ptiO2 monitoring were evaluated. Median ICP, CPP, and ptiO2 at baseline were 12 ± 6.1 mm Hg, 86 ± 17.1 mm Hg, and 27 ± 14.3 mm Hg, respectively. Values for ICP, CPP, and ptiO2 did not change significantly when comparing mean values before, during, and after therapy. Conclusions Based on ptiO2 measurements, our data provide new information about the feasibility and safety of physiotherapy in patients with severe brain diseases.

Impact of External Ventricular Drainage Volumes on Shunt Dependency after Subarachnoid Hemorrhage.

Background The indication for and the timing of a permanent shunt operation in patients following acute hydrocephalus (HC) after subarachnoid hemorrhage (SAH) remains controversial because risk factors for chronic HC fail to predict permanent shunt dependency. The amount of cerebrospinal fluid (CSF) drained via an external ventricular drain (EVD) may predict shunt dependency. Methods We conducted a retrospective study of our HC database from January 2006 to December 2011. All patients receiving an EVD due to acute HC after SAH were analyzed. The daily amount of drained CSF was documented until the EVD was removed or converted to a permanent shunt either immediately or during a follow-up period of 6 months. Results A total of 139 patients (48 male, 91 female; mean age: 57 ± 14 years) were eligible for the study. Mean duration of EVD was 16 ± 10 days (range: 4-60 days). A permanent shunt was necessary in 32% of cases (n = 45). The mean daily CSF volume was 139 ± 17 mL (range: 15-460 mL). Using repeated-measures analysis of variance, there was a significant difference of daily drained CSF volumes between both the groups in the first 15 days after the EVD. Conclusion Our results suggest that the daily amount of external CSF drainage volume in the acute state of SAH might influence the development of HC.

TGF beta1 and TGF beta2 and their role in posthemorrhagic hydrocephalus following SAH and IVH.

OBJECTIVE: Posthemorrhagic hydrocephalus (pHC) is a serious complication following subarachnoid hemorrhage (SAH) and intraventricular hemorrhage (IVH). Besides known clinical predictors, different cytokines have drawn attention to the development of chronic hydrocephalus. Transforming growth factor (TGF) ß1 and TGF ß2 are involved in fibrogenesis, scar formation, cell survival, and tissue differentiation and may play a role in the occurrence of pHC. TGF ß1 is stored in platelets in large amount and is released in the cerebrospinal fluid (CSF) after SAH and IVH. Both TGF ß1 and TGF ß2 can be expressed by various intracranial cells. METHODS: TGF ß1 and ß2 were measured in CSF and blood samples of 42 patients with SAH or IVH with acute hydrocephalus during the first 10 days after ictus. Furthermore, albumin was measured in CSF as an indicator for the amount of blood. Patients were categorized as developing pHC requiring shunt treatment or not-developing pHC within 6 months. RESULTS: After adjusting for age, SAH resulted significantly more often in pHC than did IVH. Plasma levels of TGF ß1 showed a marked increase over time, whereas CSF levels of TGF ß1 constantly decreased. The time course of TGF ß1 and albumin in CSF was paralleled and did not correlate with the development of shunt dependent pHC. Also, TGF ß1 plasma concentrations did not correlate with shunt dependent pHC. TGF ß2 concentrations in plasma showed stable values over time without any variations. TGF ß2 in CSF described a parabolic course with a peak at day 6 after ictus. No correlation was found concerning TGF ß2 in plasma or CSF and shunt dependent pHC. CONCLUSION: TGF ß1 in CSF is derived by platelets from the cisternal or ventricular clot. TGF ß2 in CSF is derived as a general reaction of traumatized brain tissue. These data do not confirm a crucial role of TGF ß1 and TGF ß2 release in the development of pHC.

Embryonic cardiomyocyte expression of endothelial genes.

Vertebrate precardiac mesoderm contains cells destined to become cardiomyocyte or endothelial cells. To determine the stability of these phenotypes freshly isolated embryonic day (E) 2.5-E6 chicken hearts were immunostained for myosin heavy chain (MyHC) to identify cardiomyocytes, and von Willebrand factor (vWF) and Flk-1 to identify endothelial cells. At E2.5-E3, 90% of cells express only MyHC and 6% express only vWF/Flk-1. However, 2% MyHC+ cells in E2.5-E3 hearts and 0.3% in E4-E6 hearts, also express vWF/Flk-1; and when cultured 3 days, >40% of the MyHC+ cells express vWF/Flk-1, but they do not express Vezf1, vascular endothelial cadherin, or Tie2. Thus, only a subset of endothelial genes are induced in cultured cardiomyocytes. While the subsequent developmental fate of embryonic heart cells exhibiting a vWF+/MyHC+ phenotype is unknown, analysis of this phenotype may provide information pertinent to mechanisms of cell phenotype stability, cellular transdifferentiation, and induction of stable cell types from embryonic stem cells.

BMP induction of cardiogenesis in P19 cells requires prior cell-cell interaction(s).

Mouse P19 embryonal carcinoma cells undergo cardiogenesis in response to high density and DMSO. We have derived a clonal subline that undergoes cardiogenesis in response to high density, but without requiring exposure to DMSO. The new subline retains the capacity to differentiate into skeletal muscle and neuronal cells in response to DMSO and retinoic acid. However, upon aggregation, these Oct 4-positive cells, termed P19-SI because they "self-induce" cardiac muscle, exhibit increased mRNAs encoding the mesodermal factor Brachyury, cardiac transcription factors Nkx 2.5 and GATA 4, the transcriptional repressor Msx-1, and cytokines Wnt 3a, Noggin, and BMP 4. Exposure of aggregated P19-SI cells to BMP 4, a known inducer of cardiogenesis, accelerates cardiogenesis, as determined by rhythmic beating and myosin staining. However, cardiogenesis is severely inhibited when P19-SI cells are aggregated in the presence of BMP 4. These results demonstrate that cell-cell interaction is required before P19-SI cells can undergo a cardiogenic response to BMP 4. A concurrent increase in the expression of Msx-1 suggests one possible process underlying the inhibition of cardiogenesis. The phenotype of P19-SI cells offers an opportunity to explore new aspects of cardiac induction.

Human umbilical vein endothelial cells fuse with cardiomyocytes but do not activate cardiac gene expression.

It was recently reported that human umbilical endothelial vein cells (HUVECs) transdifferentiate and express cardiac genes when co-cultured with rat neonatal cardiomyocytes (Condorelli et al. (2001)). If substantiated and optimized, this phenomenon could have many therapeutic applications. We re-investigated the HUVEC-rat neonatal cardiomyocyte co-culture system but detected cardiomyocyte markers (sarcomeric myosin) in only 1.2% of the cells containing nuclei that were immuno-positive for human nuclear antigen (HNA); and the frequency of such cells was not enhanced in co-cultures containing more embryonic cardiomyocytes. Because the majority of HNA-positive/myosin-positive cells were binucleated, we tested the hypothesis that these cells resulted from HUVEC-cardiomyocyte fusion rather than from HUVEC transdifferentiation. Analysis with a Cre/lox recombination assay indicated that virtually all HUVECs containing cardiac markers had fused with cardiomyocytes. To determine whether human cardiomyocyte genes are activated at low levels in HUVEC-cardiomyocyte co-cultures, quantitative RT-PCR was performed with primers specific for human beta-MyHC and cTnI. We found no evidence for transcriptional activation of these genes. None of our data support conversion of HUVECs to cardiomyocytes.