Can Chiari malformation negatively affect higher mental functioning in developmental age?

Chiari type I malformation (CMI) has been implicated to cause cognitive impairment. Unusual for a craniovertebral junction (CVJ) anomaly, this phenomenon is postulated to be related to microstructural changes across the brain. However, this has not been confirmed in a longitudinal study, in bony CVJ anomalies, or in the context of quality of life (QOL). This study aimed to analyze cognition, QOL, and diffusion tensor imaging (DTI) metrics before and after surgery for congenital CVJ anomalies and evaluate their correlations with conventional clinico-radiological factors. Fifty-seven patients with congenital CVJ anomalies-CMI, atlantoaxial dislocation (AAD), and basilar invagination (BI)-were evaluated in this prospective longitudinal study over 3 years with a neuropsychological battery, QOL and functional scores, and DTI metrics. A total of 43 patients (23 with CMI; 20 with AAD or BI) with 1-year postsurgical data were included in the final analysis. Cognitive dysfunction in one or more domains was noted in 15 (65%) of the patients with CMI and 16 (80%) of the patients with AAD/BI. Memory and visual motor perception were the most-affected domains in both the cohorts. At the 1-year follow-up, the proportion of patients demonstrating an overall cognitive dysfunction did not change significantly ( P > .05). All patients demonstrated significant postoperative improvement in functional and QOL scores at follow-up. DTI metrics improved in many regions postoperatively, but did not correlate with functional or cognitive changes ( P > .05). Cognition is affected in a majority of patients with CMI, AAD, or BI. These patients experience good functional and QOL outcomes after surgery but most of them continue to exhibit cognitive impairment. DTI metrics improve after surgery, but do not correlate with cognitive changes. These findings underline the multidimensional nature of the pathology of these anomalies that complicate achieving the concept of a "successful" surgery.

It has been well demonstrated that the cerebellum is associated with cognitive and affective processing as well as the traditionally conceptualized motor function. In the present chapter, we explore the behavioral and neurobiological implications of a common congenital cerebellar condition, Chiari malformation Type I, on cognitive and affective processing. We also emphasize the associations between Chiari-related chronic pain, cognitive dysfunction, and emotion dysregulation. Based on our review of the literature, we argue that chronic pain can account for a substantial amount of the cognitive dysfunction and emotion dysregulation in Chiari malformation Type I. Yet, there also exists aspects of Chiari-related cognitive dysfunction and emotion dysregulation that appear to be at least partially independent of chronic pain and more directly associated with abnormalities in cerebrospinal fluid flow dynamics and cerebro-cerebellar communication pathways.

The prevalence of sleep-disordered breathing (SDB) reported in the literature for Chiari malformation type 1 (CM1) is uniformly high (24% to 70%). In Canada, there is limited access to pediatric polysomnography (PSG). Therefore, the identification of clinical features would be invaluable for triaging these children. To identify demographic features, clinical symptoms/signs and radiological findings associated with SDB in a large pediatric cohort with CM1. A retrospective review was conducted on children with CM1 who underwent baseline PSG. Data were collected on patient demographics (age, sex, weight, height, body mass index), clinical symptoms (chart review and clinical questionnaires), diagnostic imaging of the brain and cervicothoracic spine, and medical history at the time of referral. A total of 68 children were included in the review. The mean (± SD) age of the children at the time of PSG was 7.33 ± 4.01 years; 56% (n=38) were male. There was a 49% prevalence of SDB in this cohort based on the overall apnea-hypopnea index. Obstructive sleep apnea was the predominant type of SDB. Tonsillar herniation was significantly correlated with obstructive apnea-hypopnea index (r=0.24; P=0.036). A direct relationship between the degree of cerebellar tonsillar herniation and obstructive sleep apnea was demonstrated. However, further prospective studies that include neurophysiological assessment are needed to further translate the central nervous system imaging findings to predict the presence of SDB.

The role of the cerebellum in cognitive function and psychiatric symptoms is poorly understood and particularly understudied in patients with cerebellar pathologies such as Chiari malformation type I (CM-I). Additionally, it is unclear if interventions targeted toward the cerebellum might impact these life-altering symptoms. The authors sought to characterize pre- and postoperative cognitive and psychiatric function in CM-I patients as evidence for targeted cerebellar treatment for some cognitive and psychiatric conditions. This prospective study included surgical patients with CM-I who reported cognitive or psychiatric dysfunction. Patients completed a preoperative assessment and a parallel assessment 6 months following surgery. Neuropsychological evaluations included a 90-minute standardized assessment of cognitive function across multiple domains and a self-reported assessment of psychiatric symptoms. This clinical sample consisted of 54 patients (mean age 34.17 years, median 14.15 years). Any patient demonstrating preoperative performance below 3.5 SDs within any cognitive domain was excluded (n = 1). All patients underwent preoperative neuropsychological assessment comprising standard clinical tests of processing speed, attention, memory, executive function, and psychiatric symptoms. Preoperatively, CM-I patients performed significantly worse than a representative normative sample on measures of executive function and visuospatial memory and reported more psychiatric symptoms across all domains. On postoperative assessment, 89% of patients showed clinically significant improvements (> 1 SD) in cognitive and/or psychiatric domains. The authors demonstrate significant, often unrecognized, impairments in cognitive function and psychiatric symptoms in a cohort of CM-I patients. Following targeted surgical posterior fossa decompression, these symptoms improved, suggesting that at least in a subgroup of symptomatic CM-I patients, these symptoms may be treatable. This study highlights the potential role of the cerebellum in cognitive and psychiatric dysfunction.

Comparison of Clinical and Radiographic Outcomes for Posterior Fossa Decompression with and without Duraplasty for Treatment of Pediatric Chiari I Malformation: A Prospective Study.

Chiari Malformation Type I (CM-I) is defined as cerebellar tonsil displacement more than 5mm below the foramen magnum. This displacement can alter cerebrospinal fluid flow at the cervicomedullary junction resulting in Valsalva-induced headaches and syringomyelia and compress the brainstem resulting in bulbar symptoms. However, little is known about cognitive and psychological changes in CM-I. To prospectively assess cognitive and psychological performance in CM-I and determine whether changes occur after surgical decompression. Blinded evaluators assessed symptomatic CM-I patients ages ≥18 with a battery of neuropsychological and psychological tests. Testing was conducted preoperatively and 6 to 18 mo postoperatively. Data were converted to Z-scores based on normative data, and t-tests were used to analyze pre-post changes. A total of 26 patients were included, with 19 completing both pre- and post-op cognitive assessments. All patients had resolution of Valsalva-induced headaches and there was improvement in swallowing dysfunction (P<.0001), ataxia (P=.008), and sleep apnea (P=.021). Baseline performances in visual perception and construction (z = -1.11, P=.001) and visuospatial memory (z = -0.93, P=.002) were below average. Pre-post comparisons showed that CM-I patients had stable cognitive and psychological functioning after surgery, without significant changes from preoperative levels. CM-I patients had below average performance in visuospatial and visuoconstructional abilities preoperatively. Prospective longitudinal data following surgery demonstrated improved neurologic status without any decline in cognition or psychological functioning. Routine pre- and postoperative formal neuropsychological assessment in CM-I patients help quantify cognitive and behavioral changes associated with surgical decompression.

Despite significant advances in diagnostic and surgical techniques, the surgical management of Chiari malformation type I (CM-I) with associated syringomyelia remains controversial, and the type of surgery performed is surgeon dependent. This study's goal was to determine the feasibility of a prospective, multicenter, cohort study for CM-I/syringomyelia patients and to provide pilot data that compare posterior fossa decompression and duraplasty (PFDD) with and without tonsillar reduction. Participating centers prospectively enrolled children suffering from both CM-I and syringomyelia who were scheduled to undergo surgical decompression. Clinical data were entered into a database preoperatively and at 1-2 weeks, 3-6 months, and 1 year postoperatively. MR images were evaluated by 3 independent, blinded teams of neurosurgeons and neuroradiologists. The primary endpoint was improvement or resolution of the syrinx. Eight clinical sites were chosen based on the results of a published questionnaire intended to remove geographic and surgeon bias. Data from 68 patients were analyzed after exclusions, and complete clinical and imaging records were obtained for 55 and 58 individuals, respectively. There was strong agreement among the 3 radiology teams, and there was no difference in patient demographics among sites, surgeons, or surgery types. Tonsillar reduction was not associated with > 50% syrinx improvement (RR = 1.22, p = 0.39) or any syrinx improvement (RR = 1.00, p = 0.99). There were no surgical complications. This study demonstrated the feasibility of a prospective, multicenter surgical trial in CM-I/syringomyelia and provides pilot data indicating no discernible difference in 1-year outcomes between PFDD with and without tonsillar reduction, with power calculations for larger future studies. In addition, the study revealed important technical factors to consider when setting up future trials. The long-term sequelae of tonsillar reduction have not been addressed and would be an important consideration in future investigations.

To examine the relationship between neonatal, periventricular brain damage and visuomotor performance in extremely-low-birthweight (ELBW) children of normal intelligence whose birthweights were appropriate for gestational age (AGA). Seventy-eight ELBW and 23 control children, all six years of age, completed two "motor-free" tests of visual spatial ability and three tests requiring visuomotor control. Full-term control children outperformed ELBW children with periventricular brain damage on all three tests requiring visuomotor guidance. No group differences were found on two "motor-free" tests of visual spatial ability. ELBW children without periventricular brain damage performed in a manner indistinguishable from controls on all tests included in this study. The findings indicate that the presence and severity of periventricular brain injury are important factors to consider in predicting visuomotor development in ELBW children.

The most appropriate surgical technique for posterior fossa decompression in Chiari malformation (CM) remains a matter of debate. Intraoperative electrophysiological studies during posterior fossa decompression of Type I CM (CM-I) aim to shed light on the entity's pathomechanism as well as on the ideal extent of decompression. The existing reports on this issue state that significant improvement in conduction occurs after craniotomy in all cases, but additional durotomy contributes a further improvement in only a minority of cases. This implies that craniotomy alone might suffice for clinical improvement without the need of duraplasty or even subarachnoid manipulation at the level of the craniocervical junction. In contrast to published data, the authors describe the case of a 32-year-old woman who underwent surgery for CM associated with extensive cervicothoracic syringomyelia and whose intraoperative somatosensory evoked potentials (SSEPs) did not notably improve after craniotomy or following durotomy; rather, they only improved after opening of the fourth ventricle and restoration of CSF flow through the foramen of Magendie. Postoperatively, the patient recovered completely from her preoperative neurological deficits. To the authors' knowledge, this is the first report of significant SSEP recovery after opening the fourth ventricle in the decompression of a CM-I. The electrophysiological and operative techniques are described in detail and the findings are discussed in the light of available literature. The authors conclude that there might be a subset of CM-I patients who require subarachnoid dissection at the level of the craniocervical junction to benefit clinically. Prospective studies with detailed electrophysiological analyses seem warranted to answer the question regarding the best surgical approach in CM-I decompression.

Objectives: In Chiari malformation type I (CIM), the cerebellar tonsils and the medial parts of the inferior cerebellar lobules are displaced downward through the foramen magnum into the upper cervical spinal canal. The primary surgical treatment for the Chiari I malformation is foramen magnum decompression. This study was undertaken to assess the clinical outcome in terms of clinical symptoms improvement in patients with Chiari malformation type I treated with foramen magnum decompression with duraplasty vs. primary repair of dura.Materials and Methods: A total of 32, 24 patients retrospectively and 8 cases prospectively were studied after being diagnosed and operated on for Chiari malformation type I. Patients with Chiari types II, III, and IV were not allowed to participate. Before and one year after surgery, a questionnaire was utilized to measure improvements in neck pain and impairment caused by it, head aches and disability caused by it, and overall health. The findings of both groups' questionnaires were analysed and compared.

Paroxysmal Neuropathic Pruritus in Patients With Chiari Malformation Type I: A Rare Phenotype

If cerebrospinal fluid (CSF) human immunodeficiency virus (HIV) RNA levels are elevated before the development of neuropsychological (NP) impairment, such an observation would support prospective monitoring of CSF HIV RNA levels as well as therapeutic interventions designed to lower CSF HIV levels. To determine whether increased CSF HIV RNA levels at an earlier time predict subsequent progression to NP impairment in HIV-infected subjects. We examined 139 subjects in a prospective cohort study. Comprehensive NP, neuromedical, and laboratory evaluations were performed at initial and follow-up visits at least 6 months apart. Human immunodeficiency virus RNA levels in plasma and CSF were measured with a commercially available, polymerase chain reaction-based assay. To assess the robustness of our findings, we analyzed changes in NP performance over time in 2 ways. First, we used masked clinical ratings of global NP performance to identify individuals who were initially NP normal, and then determined, in a similarly blinded fashion, which of these subjects subsequently became NP impaired. Second, in a separate analysis, we assessed change in subjects' raw scores on each of a series of NP test measures between baseline and follow-up. Among subjects who were not impaired at the initial visit, higher levels of HIV RNA in CSF significantly predicted progression to global NP impairment at the follow-up evaluation. Cerebrospinal fluid HIV RNA levels outperformed other clinical and laboratory measures in predicting progression to NP impairment. Higher CSF HIV RNA levels were associated with worsening performance on tests of attention, learning, and motor function. Because elevated CSF HIV RNA levels (>or=200 copies/mL) predict subsequent progression to NP impairment, monitoring of CSF viral load and therapy to reduce CSF HIV RNA levels may be clinically warranted, even if impairment is not identified at the time of lumbar puncture.

Children with nephropathic cystinosis (NCTN) have evidence of defective intellectual functions and behavioral disorders. This prospective study was performed to detect the cognitive dysfunctions in patients with this rare hereditary lysosomal storage disease, define their behavioral phenotypes, and study the findings on magnetic resonance imaging (MRI) of the brain. Thirteen patients with confirmed diagnosis of cystinosis (mean age±SD 5.9±3.0, range 1.5-12 years) were subjected to the Stanford Binet test, Porteus Maze test, Child Behavior Checklist, and MRI brain. Thirteen age- and sex-matched children served as the control subjects (mean age±SD 5.9±2.9, range 1.7-12 years). The intelligence quotient (IQ) was significantly lower in patients with cystinosis (P<0.001), with a significant defect in verbal (language, memory, and comprehension) and non-verbal abilities (visual perception and visiospatial and motor performance). A discrepancy between both abilities was detected--the non-verbal ability being lower; however, it did not reach statistical significance. Furthermore, analysis revealed the visiospatial ability to be significantly lower compared to the visual perception. In comparison to healthy controls, children with NCTN had evidence of increased incidence of behavioral problems, mainly social (P=0.023). An MRI of the brain revealed varying degrees of atrophic changes in seven patients. Patients with NCTN need a wider scope of attention and care, encompassing not only the metabolic multisystem derangement, but also the neuropsychological impairment in the context of multidisciplinary management. This approach is crucial in formulating comprehensive plans for social and educational rehabilitation.

Transforming growth factor 1 (TGF-1) is an anti-inflammatory cytokine that is expressed in different regions of the mammalian brain, and at all developmental ages. This cytokine can modulate neuron differentiation and survival, and also participate in the tissular response to injury. Based on clinical evidence, different approaches have been used to study the role of TGF-1 on modulating brain function and behavior. Here, we review evidence showing a role of TGF-1 in circadian rhythms, locomotion, sociability and depression-related behaviors. For these behaviors, suprachiamatic, hippocampal and cerebellar expression of TGF-1 have been manipulated. Further studies are required to extend these results to other brain regions and different behaviors, but so far evidence points to a role of TGF-1 on behavior disorders such as schizophrenia, depression and autism.

Although epilepsy is defined by the occurrence of spontaneous epileptic seizures, a large body of evidence indicates that epilepsy is linked to a spectrum of behavioral, psychiatric, and cognitive disorders as well as to sudden death. Explanations for these associations include the following: (1) The effects of structural lesions that may impair the functions subserved by the regions of the brain involved in the lesion. (2) The effects of seizure activity that may begin well before a clinical seizure occurs and may persist long after it is over, raising questions about what truly constitutes "interictal." In addition, encephalopathic effects of epilepsy in infancy during critical periods in development may be particularly severe and potentially irreversible. (3) Shared mechanisms underlying seizures as well as these other disorders in the absence of structural lesions or separate diseases of the central nervous system (CNS). Epidemiologic and clinical studies demonstrate the elevated risk of cognitive, psychiatric, and behavioral disorders not just during but also prior to the onset of epilepsy (seizures) itself. These may outlast the active phase of epilepsy as well. The mounting evidence argues strongly for the recognition of epilepsy as part of a spectrum of disorders and against the notion that even uncomplicated epilepsy can a priori be considered benign.