Daniele Rigamonti

Spinal epidural abscess: Contemporary trends in etiology, evaluation, and management

BACKGROUND Despite advances in neuroimaging and neurosurgical treatment, spinal epidural abscess remains a challenging problem; early diagnosis is often difficult and treatment is delayed. Optimal management is unclear, and morbidity and mortality are significant. To define contemporary trends in etiology and management, and establish diagnostic and therapeutic guidelines, we reviewed our 10-year experience with spinal epidural abscess. METHODS We examined medical records, laboratory data, radiological (CT and MRI) studies, and operative reports from 75 cases of spinal epidural abscess between 1983 and 1992. Demographic characteristics, frequency, clinical features, pathogens, risk factors, surgical and medical treatment, and outcome were analyzed. RESULTS We found a significant increase in the frequency of spinal epidural abscess over the 10-year period (p-value = 0.0195). Intravenous drug abuse was present in 28 patients (33%), diabetes mellitus in 22 patients (27%), and prior spinal surgery in 11 patients (17%). Back pain, progressive neurologic deficit, and low grade fever remained the distinguishing diagnostic features. Erythrocyte sedimentation rate was elevated in 48 of 50 patients (95%); peripheral leukocyte count was elevated in 45 patients (60%). MRI was the most effective technique for diagnosing spinal epidural abscess, revealing or suggesting the diagnosis in all 59 patients (100%) studied. Sites of spinal epidural abscess were equally distributed along the spinal axis. Staphylococcus aureus was the predominant organism (67% of patients, with 15% having a methicillin-resistant strain); 8% of patients had Streptococcal species. Most patients had open surgical drainage followed by prolonged antibiotic treatment; 22 patients were managed with antibiotics alone; 50 patients (66%) had a good clinical outcome after treatment. Multiple medical problems, prior spinal surgery, and methicillin-resistant Staphylococci were correlated with a significantly worse outcome. CONCLUSIONS The frequency of diagnosis of spinal epidural abscess is increasing. To prevent serious morbidity and mortality, early diagnosis is essential. Patients with localized back pain who are at risk for developing such abscesses or who have an increased erythrocyte sedimentation rate and/or neurologic deficit should have an immediate MRI scan with contrast enhancement. Surgical drainage and prolonged antibiotic use are the cornerstones of treatment, although selected patients may be treated conservatively.

The natural history of cavernous malformations: a prospective study of 68 patients

OBJECTIVE: Cavernous malformations are angiographically occult cerebrovascular malformations found in approximately 0.5% of the population. To help further understand the natural history of these lesions, we prospectively followed 68 patients harboring cavernous malformations. METHODS: The 68 patients in this study were all diagnosed radiographically (67 patients) or surgically (1 patient) and were entered into a patient database. Age, sex, clinical symptoms, seizure frequency, focal neurological deficits, and presence or absence of extralesional hemorrhage were all recorded at presentation. Patients were then followed prospectively to determine the rate of hemorrhage and new-onset seizures. RESULTS: The mean follow-up per patient was 5.2 years, and the total follow-up was 352.9 patient-years. There was an average of 3.4 lesions per patient. Thirteen of the patients (19%) had familial cavernous malformations. Patients with familial disease were more likely to have multiple lesions than patients with sporadic disease (85% versus 25%, respectively [P = 0.001]). Initial presentation included headache (65%), seizures (49%), and focal neurological deficit (46%). Eleven symptomatic, radiologically proven, extralesional hemorrhages occurred during the 352.9 patient-years of follow-up for an overall hemorrhage rate of 3.1% per patient-year. Female patients had a significantly higher prospective hemorrhage rate (4.2% per patient-year versus 0.9% per patient-year [P = 0.04]). A history of hemorrhage at presentation was not a risk factor for subsequent hemorrhage during follow-up. The rate of new-onset seizures was 2.4% per patient-year. CONCLUSION: The clinical presentation and prospective hemorrhage rate reported here agree well with findings of other prospective studies. This information, combined with our new-onset seizure rate, should aid clinicians caring for patients with cavernous malformations.

Hemangioblastomas of the central nervous system in von Hippel-Lindau syndrome and sporadic disease.

OBJECTIVE The presentation, screening, management, and clinical outcomes of patients who presented to our institution from 1973 to 1999 with central nervous system (CNS) hemangioblastomas in von Hippel-Lindau (VHL) syndrome and sporadic disease were analyzed. METHODS The surgical pathology database of our institution was searched to identify all patients with histologically verified CNS hemangioblastomas occurring from 1973 to 1999. The medical, radiological, surgical, pathological, and autopsy records from these patients were reviewed retrospectively and statistically analyzed. RESULTS Forty patients (21 males and 19 females) presented with CNS hemangioblastomas. Twenty-five patients (62%) harbored sporadic hemangioblastomas. Fifteen patients (38%) had VHL syndrome. These 40 patients presented with 61 hemangioblastomas (8 patients had multiple lesions). Ten patients (25%) harbored spinal cord hemangioblastomas (5 patients had multiple lesions). Patients with VHL disease tended to present with neurological symptoms and signs at a younger age than patients with sporadic disease (P = 0.09), to present with multiple lesions (53%), and to develop new lesions (rate, 1 lesion/2.1 yr). Hemangioblastomas of the spinal cord were more prevalent in patients with VHL syndrome (P = 0.024). Neuroradiological screening of patients with VHL syndrome allowed identification of more than 75% of new lesions before they became symptomatic. Sixty-six surgical procedures were performed (12 patients required multiple operations). Six patients with VHL syndrome required surgery for new lesions. Surgical complications occurred in six patients (15%). Symptom resolution or arrest of progression at 1 year was documented in 88% of patients. Recurrence of symptoms from partially resected lesions occurred in eight patients (20%). No deaths associated with surgery occurred. One patient with sporadic disease and one patient with VHL syndrome (5%) died as a result of late medical complications from CNS hemangioblastomas. CONCLUSION Surgical outcomes for patients with CNS hemangioblastomas are favorable. However, management of hemangioblastomas is a more difficult and prolonged endeavor for patients with VHL syndrome. In patients with VHL syndrome, neuroradiological screening allows identification of lesions before they become symptomatic. Because patients with VHL syndrome are at risk for development of new lesions, they require lifelong follow-up.

Diagnosis, treatment, and analysis of long-term outcomes in idiopathic normal-pressure hydrocephalus.

OBJECTIVE The response to shunt surgery for idiopathic normal-pressure hydrocephalus (INPH) is variable because INPH is difficult to distinguish from other conditions causing the same symptoms. To date, no clinical picture or diagnostic test can distinguish INPH or predict response to cerebrospinal fluid (CSF) shunt surgery. We reviewed our 10-year experience with INPH to characterize long-term outcome and to identify independent predictors of outcome after shunt surgery. METHODS Patients were classified as having INPH only if they had: 1) ventriculomegaly, 2) two or more INPH clinical features, 3) no risk factor for secondary normal-pressure hydrocephalus, 4) A- or B-waves on CSF pressure monitoring, and 5) clinical improvement during a 3-day CSF drainage trial via a spinal catheter. Independent predictors of outcome were assessed via a multivariate proportional hazards regression analysis. RESULTS One hundred thirty-two patients underwent 179 shunt surgeries. Forty-four (33%), 79 (60%), and 99 (75%) patients demonstrated objective improvement 3, 6, and 24 months after shunt surgery, respectively. Gait improved first in 88 (93%) patients. Dementia and urinary incontinence were twofold less likely to improve. Radiological evidence of corpus callosum distension, gait impairment as the primary symptom, and shorter duration of INPH symptoms predicted improvement. Duration of symptoms and gait as the primary symptom were independent predictors by multivariate analysis. CONCLUSION INPH can be diagnosed accurately with CSF pressure monitoring and CSF drainage via a spinal catheter. CSF shunting is safe and effective for INPH with a long-term shunt response rate of 75%. Independent predictors of improvement are the presence of gait impairment as the dominant symptom and shorter duration of symptoms.

The diagnosis and treatment of idiopathic normal pressure hydrocephalus

Idiopathic normal pressure hydrocephalus (INPH) is a syndrome that is characterized by gait impairment, cognitive decline and urinary incontinence, and is associated with ventriculomegaly in the absence of elevated cerebrospinal fluid (CSF) pressure. There is significant variation in the clinical presentation and progression of this disorder, and its diagnosis often represents a challenge for neurologists and neurosurgeons. Various supplemental tests, including the CSF tap test, external CSF drainage via spinal catheter, and CSF outflow resistance determination, can improve the accuracy of predicting a response to surgical treatment. CSF shunting provides significant symptom improvement in the majority of appropriately evaluated patients. In 2005, an international study group published evidence-based guidelines for the diagnosis and management of INPH. This review will highlight the clinical presentation, radiographic findings, supplemental prognostic tests, differential diagnosis, surgical treatment and outcomes of INPH.

Genetics of human hydrocephalus

Human hydrocephalus is a common medical condition that is characterized by abnormalities in the flow or resorption of cerebrospinal fluid (CSF), resulting in ventricular dilatation. Human hydrocephalus can be classified into two clinical forms, congenital and acquired. Hydrocephalus is one of the complex and multifactorial neurological disorders.A growing body of evidence indicates that genetic factors play a major role in the pathogenesis of hydrocephalus. An understanding of the genetic components and mechanism of this complex disorder may offer us significant insights into the molecular etiology of impaired brain development and an accumulation of the cerebrospinal fluid in cerebral compartments during the pathogenesis of hydrocephalus. Genetic studies in animal models have started to open the way for understanding the underlying pathology of hydrocephalus. At least 43 mutants/loci linked to hereditary hydrocephalus have been identified in animal models and humans. Up to date, 9 genes associated with hydrocephalus have been identified in animal models. In contrast, only one such gene has been identified in humans. Most of known hydrocephalus gene products are the important cytokines, growth factors or related molecules in the cellular signal pathways during early brain development. The current molecular genetic evidence from animal models indicate that in the early development stage, impaired and abnormal brain development caused by abnormal cellular signaling and functioning, all these cellular and developmental events would eventually lead to the congenital hydrocephalus.Owing to our very primitive knowledge of the genetics and molecular pathogenesis of human hydrocephalus, it is difficult to evaluate whether data gained from animal models can be extrapolated to humans. Initiation of a large population genetics study in humans will certainly provide invaluable information about the molecular and cellular etiology and the developmental mechanisms of human hydrocephalus.This review summarizes the recent findings on this issue among human and animal models, especially with reference to the molecular genetics, pathological, physiological and cellular studies, and identifies future research directions.

Cavernous malformations: natural history, diagnosis and treatment

Cavernous malformations (CMs) consist of dilated vascular channels that have a characteristic appearance on MRI. CMs are usually found intracranially, although such lesions can also affect the spinal cord. Individuals with CMs can present with epilepsy and focal neurological deficits or acute intracranial hemorrhage. In many cases, however, patients with such lesions are asymptomatic at diagnosis. Furthermore, several natural history studies have documented that a substantial proportion of asymptomatic CMs follow a benign course. Surgical resection is recommended for CMs that require intervention. Radiosurgery has been advocated for many lesions that have not been easily accessible by conventional surgery. The outcomes of radiosurgery and surgery for deep lesions, however, vary widely between studies, rendering treatment recommendations for such CMs difficult to make. In addition to reviewing the literature, this article will discuss the current understanding of lesion pathophysiology and explore the controversial issues in the management of CMs, such as when to use radiosurgery or surgery in deep-seated lesions, the treatment of epilepsy, and the safety of anticoagulation.

Normal pressure hydrocephalus: long-term outcome after shunt surgery

Background/objective: Little is known about the long-term clinical course and management of patients with normal pressure hydrocephalus (NPH) treated by cerebrospinal fluid (CSF) shunting. Methods: We retrospectively reviewed records of 55 patients diagnosed with idiopathic NPH (INPH) and treated with CSF shunts, all of whom were followed for more than 3 years after the original shunt surgery. At each annual follow-up visit, the patient was assessed by Folstein Mini Mental State Examination, detailed clinical evaluation of gait and assessment of headache, cognition, gait or urination, as assessed by the patient and relatives. Results: The mean duration of follow-up was 5.9±2.5 years. There was an overall sustained improvement among all symptoms. Gait showed the highest maintenance of improvement over baseline (83% at 3 years and 87% at the last analysed follow-up of 7 years), cognition showed intermediary improvement (84% and 86%, respectively), and urinary incontinence showed the least improvement (84% and 80%, respectively). Fifty-three percent of patients required shunt revisions. Indications for revision included shunt malfunction (87%), infection (10%) and change of shunt configuration (3%). Overall, 74% revisions resulted in clinical improvement. Conclusions: Clinical improvement of patients with NPH can be sustained for 5–7 years in some patients with NPH, even if shunt revision surgery is needed multiple times. With earlier diagnosis and treatment of NPH and the increasing lifespan of the ageing population, the need for long-term follow-up after shunt surgery for NPH may be greater than it was in the past. Monitoring, identification and treatment of shunt obstruction is a key management principle.

Epidural abscesses of the CNS

Epidural abcessess can involve the intercranial or spinal compartments and can result in potentially devastating neurological injuries. Although rare, incidence of spinal epidural abscesses (SEAs) is increasing as predisposing factors such as injected-drug use, chronic immunosuppression, and spinal surgery become more common. Whereas symptoms of SEAs can include fever, back pain, and neurological dysfunction, the presentation of intracranial epidural abscesses (ICEAs) is less well defined. Neuroimaging narrows the potential diagnoses and enables prompt empirical therapy until specific microbiological diagnosis is made. Surgical intervention is an integral part of treatment for epidural abscesses in patients with neurological symptoms or who have not responded to medical management. Prognosis for both SEAs and ICEAs is typically poor because of delayed diagnosis and intervention and is dependent on the neurological status at the time of diagnosis. Increased clinical awareness can greatly improve outcomes by helping to diagnose patients earlier.

Cognitive impairments after surgical repair of ruptured and unruptured aneurysms

OBJECTIVES To determine the frequency and severity of neuropsychological impairments associated with aneurysmal subarachnoid haemorrhage, and associated with repair of intracerebral aneurysms. METHODS Two groups of patients who underwent repair of intracerebral aneurysms were studied: patients with unruptured aneurysms (n=20) and patients with ruptured aneurysms (n=27). All patients were administered a battery of standardised neuropsychological tests about 3 months after surgery. A subset of 12 patients with unruptured aneurysms were administered the battery both before and after elective repair of the aneurysm(s). A subset of six patients with ruptured aneurysms were given the test at both 3 months and 1 year after surgery. RESULTS As previously reported for patients with ruptured aneurysms, patients with both ruptured and unruptured aneurysms performed, as a group, significantly below published norms on many of the neuropsychological tests after surgery. However, there were significant differences between preoperative and postoperative performance in the unruptured aneurysm group only on a few tests: measures of word fluency, verbal recall, and frontal lobe function. Performance of patients with ruptured aneurysms was significantly below that of patients with unruptured aneurysms only on a few tests of verbal and visual memory. In addition, group differences compared with published norms reflected severely impaired performance by a minority of patients, rather than moderately impaired performance in a majority of patients. CONCLUSIONS Although patients who undergo repair of ruptured aneursyms perform, as a group, below published norms on many neuropsychological tests, significant impairments are seen in a minority of patients. Some of the impairments are associated with subarachnoid haemorrhage, whereas others (found in patients who underwent repair of unruptured aneurysms) are due to general effects of neurosurgery and perioperative management. Finally, some of the postoperative deficits are merely a reflection of premorbid weaknesses.