Baseline neuropsychological profile and cognitive response to cerebrospinal fluid shunting for idiopathic normal pressure hydrocephalus

OBJECTIVE: To evaluate neurocognitive changes and predict neurocognitive outcome after ventriculoperitoneal shunting for idiopathic normal pressure hydrocephalus (INPH). BACKGROUND: Reports of neurocognitive response to shunting have been variable and studies that predict cognitive outcomes after shunting are limited. We reviewed our experience with cognitive outcomes for INPH patients who were selected for shunting based on abnormal cerebrospinal fluid (CSF) pressure monitoring and positive response in any of the NPH symptoms following large volume CSF drainage. METHODS: Forty-two INPH patients underwent neurocognitive testing and Folstein Mini-Mental State Examination (MMSE) prior to shunting. Neurocognitive testing or MMSEwere performed at least 3 months after shunt insertion. Significant improvement in a neurocognitive subtest was defined as improvement by one standard deviation (1 SD) for the patient's age, sex and education level. Significant improvement in overall neurocognitive outcome was defined as a 4-point improvement in MMSE or improvement by 1 SD in 50% of the administered neurocognitive subtests. Nonparametric tests were used to assess changes. Predictors of outcome were assessed via logistic regression analysis. RESULTS: Twenty-two patients (52.3%) showed overall neurocognitive improvement, and significant improvement was seen in tests of verbal memory and psychomotor speed. Predictive analysis showed that patients scoring more than 1 SD below mean at baseline on verbal memory immediate recall were fourfold less likely to show overall cognitive improvement, and sixfold less likely if also associated with visuoconstructional deficit or executive dysfunction. Verbal memory scores at baseline were higher in patients who showed overall cognitive improvement. CONCLUSIONS: Shunting INPH patients on the basis of CSF pressure monitoring and drainage response shows a significant rate of cognitive improvement, and baseline neurocognitive test scores may distinguish patients likely to respond to shunt surgery from those who will not.     

Acute headache with meningism and xanthochromic cerebrospinal fluid.An unusual manifestation of cervical epidural abscess

We report on a 70-year-old female with acute onset of headache, meningism, xanthochromic cerebrospinal fluid, and developing laboratory parameters indicating a systemic infection. Initially, a subarachnoidal hemorrhage was assumed. However, magnetic resonance imaging showed upper cervical osteomyelitis and extending spinal epidural abscess. After application of broad systemic antibiotics, secluded abscess formation was achieved and successful neurosurgical debridement performed. The unusual cranial concentration of the complaints is probably due to the involvement of the craniocervical transition. Cervical epidural spinal abscess represents a potentially dangerous bacterial infection of the upper spine. Inadequate treatment can lead to irreversible neurological deficits. Cervical magnetic resonance imaging is an effective tool for diagnosis, since early diagnosis is important for good prognosis.     

Intraventricular vancomycin in the treatment of ventriculitis associated with cerebrospinal fluid shunting and drainage.

The results of treatment of 50 cases of ventriculitis associated with the use of cerebrospinal fluid shunts or external ventricular drains, and treated with intraventricular vancomycin, are reported. While the overall cure rate was 66% with four cases lost to follow-up, in those cases where treatment involved shunt removal, 20 mg vancomycin daily intraventricularly, and another appropriate systemic antibiotic, 22 of 24 cases were cured with two cases lost to follow-up. In those cases where the shunt was left in during treatment, results were poor and revision for blockage of the distal catheter of ventriculoperitoneal shunts was required in 44% of these. All five patients whose ventriculitis followed external ventricular drainage were cured. Despite relatively high trough levels of vancomycin in the cerebrospinal fluid, no evidence of toxicity was seen.     

Cranioplasty for patients with severe depressed skull bone defect after cerebrospinal fluid shunting.

Cranioplasty is indicated for patients with a skull bone defect. Patients may achieve subjective and objective improvements after cranioplasty. Some patients with severe brain swelling treated with decompressive craniectomy may develop hydrocephalus associated with severe brain bulging or even herniation via the skull bone defect. Consequently, these patients require a ventriculoperitoneal (V-P) shunt to relieve hydrocephalus. However, after shunting for hydrocephalus, they may develop severe sinking at the skull defect. Subsequently, when doing a cranioplasty for such a depressed defect, it may result in the dysfunction of the underlying brain, or even hematoma formation due to the large dead space. In this study, we advocate a temporary procedure to occlude the V-P shunt tube to allow the expansion of a depressed scalp flap to facilitate the subsequent cranioplasty. We report four patients with severe depression of the skull defect resulting from previous traumatic brain swelling followed by decompressive craniectomy and V-P shunting for communicating hydrocephalus. A simple subcutaneous clipping of the shunt tube was performed to allow the expansion of the depressed scalp to obliterate the dead space before the cranioplasty. All four patients obtained a satisfactory result without complications and achieved good functional recovery. A temporary occlusion of the shunt tube with an aneurysm clip before cranioplasty for patients with a severely depressed scalp flap is a simple and useful procedure. This procedure can safely and effectively eliminate the dead space between the skull plate and the dura to facilitate the cranioplasty, and thus prevent the potential complication of intracranial hematoma.     

Initial experience with antibiotic-impregnated silicone catheters for shunting of cerebrospinal fluid in children

INTRODUCTION: Infection is a major complication of cerebrospinal fluid (CSF) shunting procedures. Recently, rifampin-impregnated and clindamycin-impregnated silicone catheters have been developed in an attempt to prevent and/or reduce the incidence of shunt infections. In vitro and in vivo animal studies have shown their efficacy in reducing bacterial colonization of catheters. However, these shunts are yet to be evaluated in clinical trials and their safety and efficacy in preventing shunt infections is unknown.METHODS: Between April 2002 and April 2003, 31 children (age range 6 months to 17 years, mean 4.5 years) underwent implantation of an antibiotic-impregnated silicone catheter for CSF diversion. All surgeries were performed by a single neurosurgeon (HSM) at a single medical center. The Codman Hakim Bactiseal silicone catheter was used in all children. Thirty-two catheters were implanted in 31 children. All children have been followed since surgery (for an average of 19 months). For comparison, the previous 46 standard implanted shunts over a similar period of time were reviewed (average follow-up 31 months).RESULTS: Of the 32 implanted catheters, 11 involved placement of a new complete shunt system, 8 were distal revisions, and 13 were proximal/ventricular revisions. There were fewer early and late complications than in the standard shunt group (12.5 and 18.8% vs. 23.9 and 34.8%). There was no local reaction from implantation of the catheters. One child contaminated his distal catheter by disrupting his abdominal incision. None of the other patients have developed any evidence of shunt infection to date.CONCLUSION: Rifampin-impregnated and clindamycin-impregnated silicone catheters appear to be safe and well tolerated in children. Preliminary results suggest a low incidence of shunt infection. Longer follow-up and a larger number of patients are needed to more accurately assess the efficacy of these catheters compared with traditional silicone catheters.     

Familial amentia, unusual ventricular calcifications, and increased cerebrospinal fluid protein.

A sibship originally reported by Friedman and Roy as showing severe mental retardation, strabismus, hyperactive tendon reflexes, lalling speech, and foot deformities was restudied. Three major additional findings were noted. The cerebrospinal fluid protein concentration was increased two to three times above normal in four siblings who were available for study. Radiographs of cranial structures in three siblings showed identical pathologic intracranial calcifications which correspond in distribution to the choroid plexus. The choroid plexus was not demonstrable in one patient when radiolabeled 99m-Tc-pertechnetate was injected without perchlorate. Neuropathologic findings in one sibling included small subcortical heterotopias and atrophy of the choroid plexus with encasement by glial fibrils. These findings denote a new heredofamilial neurologic syndrome associated with mental retardation and a disorder of choroid plexus.     

Cognitive changes after cerebrospinal fluid shunting in young adults with spina bifida and assumed arrested hydrocephalus

OBJECTIVES: To establish whether surgery can improve the neuropsychological functioning of young adult patients with spina bifida and apparent clinically arrested hydrocephalus showing abnormal intracranial pressure. METHODS: Twenty three young adults with spina bifida and assumed arrested hydrocephalus (diagnosed as active or compensated by continuous intracranial pressure monitoring) underwent surgery. All patients received neuropsychological examination before surgery and 6 months later. Neuropsychological assessment included tests of verbal and visual memory, visuospatial functions, speed of mental processing, and frontal lobe functions. RESULTS: Shunt placement in this subgroup of patients improves neuropsychological functioning, especially in verbal and visual memory and attention and cognitive flexibility. CONCLUSIONS: Young adults with spina bifida and suspected non-functioning shunt or non-shunted ventriculomegaly should be carefully monitored to identify those who could benefit from shunting.     

Serum and cerebrospinal fluid cytokines in children with acute encephalopathy

BackgroundThe pathogenesis of acute encephalopathy (AE) remains unclear, and a biomarker has not been identified.MethodsLevels of 49 cytokines and chemokines, including osteopontin (OPN), were measured in serum and cerebrospinal fluid (CSF) of children with AE (n = 17) or febrile convulsion (FC; n = 8; control group). The AE group included acute necrotizing encephalopathy (n = 1), acute encephalopathy with biphasic seizures and late reduced diffusion (AESD; n = 3), clinically mild encephalitis/encephalopathy with a reversible splenial lesion (MERS; n = 4), and unclassified acute encephalopathy (UCAE; n = 9) that does not meet the criteria of syndrome classification. Five individuals with AE had neurological sequelae or death (poor prognosis), whereas 12 were alive without neurological sequelae (good prognosis).ResultsThe CSF:serum ratios of OPN, CC chemokine ligand (CCL)4, and interleukin (IL)-10 were significantly higher in AE than in FC. The CSF levels of macrophage inhibitory factor (MIF) and leukemia inhibitory factor (LIF) were significantly higher in the poor-prognosis group than in the good-prognosis group. The CSF:serum ratios of OPN were significantly higher in AESD and in MERS than in FC. The CSF:serum ratios of MIF and OPN were higher in MERS than in UCAE or FC.ConclusionOur results suggest that microglia-related cytokines and chemokines such as OPN, MIF, and LIF could be novel biomarkers of AE, in addition to the previously reported IL-10 and CCL4, and that MIF and LIF may be markers of poor prognosis.     

Apoptosis in neurones exposed to cerebrospinal fluid from patients with multiple sclerosis or acute polyradiculoneuropathy.

Primary cultures of murine cerebellar granule neurones were exposed to cerebrospinal fluid from patients with subtypes of multiple sclerosis or acute polyradiculoneuropathy (Guillain-Barré syndrome) for 2 days. Cells were then stained with Hoechst 33342 or terminal deoxynucleotidyl transferase-mediated dUTP nick-end labelling (TUNEL) to detect apoptotic bodies. The results were compared with control cultures exposed to cerebrospinal fluid from patients with no known neurological disease or deficit. There was no significant difference in the level of apoptosis induced between these controls and cultures not exposed to cerebrospinal fluid at all. Cultures exposed to cerebrospinal fluid samples from patients with relapsing-remitting multiple sclerosis did not have higher levels of apoptosis than cells exposed to controls, regardless of whether the sample was taken during relapse or remission. However, a significant increase in apoptosis was observed in cultures exposed to cerebrospinal fluid from patients with primary progressive multiple sclerosis, and apoptosis correlated with disease severity. This supports the existence of biochemical differences between subgroups of multiple sclerosis. A significant increase in apoptosis was also induced by cerebrospinal fluid samples from patients with acute polyradiculoneuropathy, suggesting the presence of neurotoxic factor(s) here also. The relevance to disease pathology is unclear.     

Idiopathic normal-pressure hydrocephalus: clinical comorbidity correlated with cerebral biopsy findings and outcome of cerebrospinal fluid shunting

Objectives

To elucidate the importance of clinically diagnosed cerebral comorbidity in idiopathic normal‐pressure hydrocephalus (INPH) and its effect on improvement after shunt surgery as well as concordance with parenchymal pathological changes described in frontal cerebral biopsy specimens.

Methods

In 28 consecutive patients diagnosed with INPH and shunted according to clinical, radiological and cerebrospinal fluid dynamic criteria, concomitant disorders were carefully registered, with special emphasis on cerebrovascular disease (CVD) and possible Alzheimer''s disease. During shunt surgery, a frontal cerebral biopsy specimen was obtained and subsequently analysed for pathological changes.

Results

One or several concurrent disorders were present in 89% of the patients, most often CVD (n = 17) and possible Alzheimer''s disease (n = 12), of which eight patients presented both, diagnosed according to the criteria of the National Institute of Neurological and Communicative Disorders and Stroke and the Alzheimer''s Disease and Related Disorders Association. The shunt success rate was 33%. A clear tendency towards increasing prevalence of CVD or Alzheimer''s disease was found in the subgroups with no improvement or clinical deterioration compared with the patients improving after shunt surgery. The presence of CVD tended towards an unfavourable shunt outcome. The pathological parenchymal changes reflected the clinical diagnoses of comorbidity, and were described in about half of the biopsy specimens, with Alzheimer''s disease (n = 7) and vascular changes (n = 7) being the most common findings. However, no significant correlation was found with the clinical diagnoses of Alzheimer''s disease and CVD. The presence of cerebral comorbidity, whether diagnosed clinically or by brain biopsy, did not preclude clinical improvement after shunt operation.

Conclusions

A high prevalence of CVD and Alzheimer''s disease was found in patients shunted for INPH, which was reflected, although less commonly, by similar neuropathological biopsy findings. No significant correlation was found between the presence of comorbidity and shunt outcome. The findings support the perception of INPH as a multiaetiological clinical entity, possibly overlapping pathophysiologically with CVD and Alzheimer''s disease.Patients with the idiopathic normal‐pressure hydrocephalus (INPH) syndrome are traditionally described as presenting a clinical triad of progressing gait disturbances, dementia and urinary urge incontinence, and with a radiologically defined hydrocephalus on computed tomography or magnetic resonance imaging.As opposed to secondary normal‐pressure hydrocephalus (NPH), no apparent precipitating factor is identified in INPH. The patients are generally older¹ and consequently more prone to have concomitant diseases. In concordance, the shunt success rate in patients with possible INPH is lower than in patients with secondary NPH,^2,3 varying from 25% to 80%.^4,5In patients not responding to shunt surgery, cerebrovascular disease (CVD) and Alzheimer''s Disease are the predominant disorders thought to mimic the INPH syndrome. This presumption is based on the fact that Alzheimer''s disease and CVD are the most common causes of dementia, and from autopsy and biopsy findings of CVD or Alzheimer''s disease in patients with INPH—including patients improving after a shunt operation.^{6,7,8,9,10,11} It has also been hypothesised that INPH shares common pathophysiology with Alzheimer''s disease¹² or CVD,^13,14,15 which only further confounds the clinical picture.Thus, the main question for the clinician contemplating a shunt operation is not whether the patient has INPH or a concurrent irreversible disorder, but whether the hydrocephalus or the presence of a non‐shunt responsive comorbidity—most often CVD or Alzheimer''s disease—is the major contributor to the symptomatology. The selection of patients for shunt surgery has become even more controversial after recent data suggesting shunt improvement in patients with no symptoms or signs of INPH but with a clinical diagnosis of Alzheimer''s disease.¹⁶In this prospective study of patients shunted for INPH according to clinical, radiological and cerebrospinal fluid (CSF) dynamic criteria, frontal cerebral biopsy specimens were obtained before the insertion of a shunt and examined for pathological parenchymal changes. Clinical comorbidity was carefully registered, and the clinical diagnoses of CVD and Alzheimer''s disease were established by a trained neurologist. The presence of concomitant disorders was correlated with shunt outcome and cerebral biopsy findings to elucidate the importance of clinical comorbidity in patients with INPH, and its effect on improvement after shunt surgery as well as concordance with the pathological cerebral parenchymal changes.     

Use of ventricular cerebrospinal fluid lactate measurement to diagnose cerebrospinal fluid infection in patients with intraventricular haemorrhage.

Early diagnosis of ventriculostomy-associated cerebrospinal fluid (CSF) infection in acute neurosurgical patients can be difficult. The use of prophylactic antibiotics in intraventricular or subarachnoid haemorrhage decreases the sensitivity of cell counts, Gram staining and bacterial culture as diagnostic tools. We prospectively collected clinical and cerebrospinal data for 16 patients with intraventricular haemorrhage, with an external ventricular drain inserted, with or without spontaneous subarachnoid haemorrhage. Three (18.8%) patients had cerebrospinal fluid infection, with appropriate changes in antibiotic regimens needed. All three patients had CSF lactate levels of >4 mmol/L (6.4 mmol/L, 7.8 mmol/L, 7.9 mmol/L). Eleven out of 13 patients without CSF infection had CSF lactate levels of below 4 mmol/L. The two patients with CSF lactate levels of 4-6 mmol/L were grade 5 subarachnoid haemorrhage patients, one with renal impairment. Using a cut-off lactate level of 4 mmol/L, the positive predictive value was 60% and negative predictive value was 100% for CSF infection. A CSF lactate level of above 4 mmol/L should prompt suspicion of CSF infection in intraventricular haemorrhage patients with an external ventricular drain.     

Ultrastructure of rectal biopsy specimens in unusual familial ataxia with cerebrospinal fluid abnormality

The ultrastructure of rectal biopsy specimens from a 60-year-old woman of unusual familial ataxia with cerebrospinal fluid abnormality was investigated. She had two male siblings similarly affected and a close consanguinity in the family. Meissner's plexus neurons, Schwann cells, fibroblasts and smooth muscle cells within the rectum contained intracytoplasmic eosinophilic inclusions (IEIs) with or without intensely eosinophilic granules. Ultrastructurally the IEIs were composed of a membrane-bound, fine granular material with or without dense cores. The IEIs resembled intracytoplasmic inclusions seen in various cells of the central nervous system from a male autopsied sibling. The clinically and morphologically similar finding in the two siblings suggests an autosomal recessive inherited metabolic disorder previously unreported.     

Lymphocyte subpopulations in blood and cerebrospinal fluid from patients with acute Guillain-Barré syndrome.

The numbers of T and B lymphocytes were determined in blood and cerebrospinal fluid (CSF) from 25 patients with acute Guillain-Barré syndrome and from 30 controls. The relative and absolute number of T lymphocytes in blood was decreased in the patient group (mean 48 +/- 2% and 947 +/- 71/mm3 compared to 66 +/- 2% and 1,381 +/- 93/mm3 in controls). Correspondingly, the number of B lymphocytes was increased (mean 37 +/- 2% and 758 +/- 75/mm3 compared to 25 +/- 2% and 580 +/- 45/mm3 in controls). In the CSF the number of T lymphocytes was increased (85.0 +/- 2.2% compared to 76.9 +/- 2.4% in controls).     

Serum and cerebrospinal fluid antibodies to Nogo-A in patients with multiple sclerosis and acute neurological disorders

Nogo-A is a protein associated with central nervous system (CNS) myelin thought to impair regenerative responses and to suppress sprouting and plastic changes of synaptic terminals. In this study, we report that serum IgM autoantibodies to the recombinant large N-terminal inhibitory domain of Nogo-A are a frequent finding in multiple sclerosis (MS) and acute inflammatory (IND) and non-inflammatory neurological diseases (OND), but not in neurodegenerative diseases (ND), systemic inflammatory disease and healthy controls. Furthermore, we demonstrate intrathecal production of anti-Nogo-A antibodies measured by increased IgG indices. Intrathecal anti-Nogo antibodies were significantly more frequent in patients with relapsing-remitting as compared to chronic progressive (CP) MS. We also found a highly significant negative correlation of these antibody responses with age indicating that they are more frequent in younger patients. We finally demonstrate that human anti-Nogo-A antibodies recognize native Nogo-A in brain extracts, oligodendrocytes and cells expressing human Nogo-A.