Congenital absence of touch does not preclude normal cognitive and socioemotional development.

Attachment theory holds that development of normal affective and social behavior requires physical contact between infant and caregiver. The elevation of touch to paramount importance has gone unchallenged because, prior to the present study, no individual with a congenital lack of somatosensation has been reported, much less studied for psychosocial development. Here we describe Kim, who since birth, has been unable to perceive touch, temperature changes, or pain on the body surface. Despite her inability to sense physical contact, Kim has above-average intelligence. She functions normally in social situations with a variety of people, recognizing emotions in herself and others and demonstrating appropriate affect. Kim experiences anxiety that appears grounded in realistic fears and uncertainties particular to her somatic insensitivity, thus serving as adaptive vigilance in reaction to an abnormal sensorium. Her normal socioemotional development, evident from an early age, likely resulted from Kim being able to appreciate her parents' loving care through gaze, movement, and hearing. In sum, Kim upends the idea of touch as critical to developing a sense of self, secure attachment, and family bonds.

Increased apathy post-interstitial laser capsulotomy for refractory obsessive-compulsive disorder.

BACKGROUND: MRI guided laser interstitial thermal therapy (M-LITT) capsulotomy has proven to be efficacious in decreasing refractory obsessive-compulsive disorder (OCD) related symptomatology yet capsulotomy either via radiosurgery or radiofrequency ablation has in some patients led to increased apathy following surgery. The current case series aims to investigate objective patient-reported change in apathy, disinhibition, depression, and executive dysfunction following anterior capsulotomy via M-LITT for OCD. METHODS: Ten consecutive patients pre- and post-M-LITT completed measures of OCD, apathy, disinhibition, executive dysfunction, and depression (Mtime between = 1.3 years; 0.42-3.7 years). Reliable Change Index (RCI) was used to evaluate change in pre- and post-M-LITT. OCD symptom response was evaluated using percent change (Y-BOCS scores: 24-34 % reduction indicating partial response; ≥35% reduction indicating full response). RESULTS: Positive post-surgical change was noted in OCD symptomatology with >65% reporting a partial or full response. However, six patients endorsed increased apathy with half of the non-responders (e.g., less than <24% score reduction on Y-BOCS) reporting increases in apathy. Patients reported relatively stable disinhibition and executive dysfunction, while over half reported a decrease in depression symptoms. Two of the non-responders and one responder endorsed increased apathy despite stable or improved depression symptoms, disinhibition, and executive dysfunction. CONCLUSIONS: Most patients in the current cohort achieved full-or-partial OCD recovery. Yet, 60% of patients also reported significant increases in apathy, despite experiencing a decrease in depression symptoms, with stable disinhibition and executive dysfunction. Despite these promising improvements in OCD symptomatology following M-LITT, further investigations of the impact of surgery and lesion location on apathy levels is clearly warranted using objective, quantifiable methods.

Cognitive outcomes in patients with essential tremor treated with deep brain stimulation: a systematic review.

Introduction: Essential tremor (ET) is a common neurological disease. Deep brain stimulation (DBS) to the thalamic ventral intermediate nucleus (VIM) or the adjacent structures, such as caudal zona incerta/ posterior subthalamic area (cZi/PSA), can be effective in treating medication refractory tremor. However, it is not clear whether DBS can cause cognitive changes, in which domain, and to what extent if so. Methods: We systematically searched PubMed and the Web of Science for available publications reporting on cognitive outcomes in patients with ET who underwent DBS following the PICO (population, intervention, comparators, and outcomes) concept. The PRISMA guideline for systematic reviews was applied. Results: Twenty relevant articles were finally identified and included for review, thirteen of which were prospective (one also randomized) studies and seven were retrospective. Cognitive outcomes included attention, memory, executive function, language, visuospatial function, and mood-related variables. VIM and cZi/PSA DBS were generally well tolerated, although verbal fluency and language production were affected in some patients. Additionally, left-sided VIM DBS was associated with negative effects on verbal abstraction, word recall, and verbal memory performance in some patients. Conclusion: Significant cognitive decline after VIM or cZi/PSA DBS in ET patients appears to be rare. Future prospective randomized controlled trials are needed to meticulously study the effect of the location, laterality, and stimulation parameters of the active contacts on cognitive outcomes while considering possible medication change post-DBS, timing, standard neuropsychological battery, practice effects, the timing of assessment, and effect size as potential confounders.

Cerebellar cognitive affective syndrome with psychotic features in a patient with hypertrophic olivary degeneration.

Objective: Hypertrophic Olivary Degeneration is a rare condition causing transneuronal degeneration of the inferior olivary nucleus. Symptoms manifest as progressively worsening palatal tremor, ataxia, and eye movement disturbances that plateau after several months. Though rarely documented in the literature of this specific condition, disconnection of the inferior olivary nucleus from the cerebellum, and cerebellar atrophy represent a pathway to developing subsequent cerebellar cognitive affective syndrome. The presented case documents the neuropsychological sequelae of a 39-year-old female with a history of hypertrophic olivary degeneration and symptoms of palatal tremor, opsoclonus myoclonus, ataxia, and delusions. Method: Review of the patient's medical records, interviews with the patient and her father, and a neuropsychological assessment battery were used to collect data. Review of currently published literature lent to case conceptualization. Results: Neuropsychological testing revealed deficits in executive functioning, attention, and language. An anomalous, fixed persecutory delusion was revealed. Conclusion: Hypertrophic olivary degeneration creates disconnection syndromes between the inferior olivary nucleus, red nucleus, and cerebellum. Late stages of the disorder cause atrophy of the inferior olivary nucleus and adjacent structures. While the motor sequela is well documented, the neuropsychological and psychiatric impact is infrequently discussed in existing literature. We present the first case to detail the neuropsychological sequelae of hypertrophic olivary degeneration and propose a mechanism for the development of cognitive impairment and psychotic features within this condition.

Case report: neuropsychological assessment in a patient with 4H leukodystrophy.

Objective: POLR3-HLD or 4H leukodystrophy is an autosomal recessive disorder characterized by hypomyelination, hypodontia, and hypogonadotropic hypogonadism, and caused by variants in POLR3A, POLR3B, POLR1C, or POLR3K genes. Neurological and non-neurological clinical features and disease severity vary. While previous studies reference variable cognition, this is the first report of 4H detailing a comprehensive neuropsychological assessment. Method: The current study presents a 20-year-old, English-speaking, right-handed, non-Hispanic White female with 12 years of education with genetically confirmed 4H POLR3B-related leukodystrophy without hormonal replacement treatment. Results: At age 4, developmental delays, ataxia, hearing loss, and abnormal dentition were present. Imaging, endocrinology, and neurologic examinations revealed hypomyelination, reduced cerebellar volume, delayed bone age density, osteopenia, and evidence of adrenarche without signs of true puberty. Neuropsychological assessment at age 20 revealed global cognitive impairment with intellectual, attention, verbal memory retrieval, construction, executive (e.g. processing speed, sustained attention) and math computation deficits, along with behavioral dysregulation. Conclusion: We present the first detailed neuropsychological assessment of a patient with 4H leukodystrophy. The neuropsychological assessment revealed cognitive and behavioral dysexecutive deficits aligning with hypomyelination observed on imaging. Further longitudinal studies are needed to shed light on the neurobehavioral presentation associated with this disorder to assist care providers, patients, and their families.

Interstitial laser anterior capsulotomy for obsessive-compulsive disorder: lesion size and tractography correlate with outcome.

BACKGROUND: Anterior capsulotomy is a well-established treatment for refractory obsessive-compulsive disorder (OCD). MRI-guided laser interstitial thermal therapy (LITT) allows creation of large, sharply demarcated lesions with the safeguard of real-time imaging. OBJECTIVE: To characterise the outcomes of laser anterior capsulotomy, including radiographical predictors of improvement. METHODS: Patients with severe OCD refractory to pharmacotherapy and cognitive-behavioural therapy underwent bilateral anterior capsulotomy via LITT. The primary outcome was per cent reduction in Yale-Brown Obsessive-Compulsive Scale (Y-BOCS) score over time. Lesion size was measured on postablation MRI. Disconnection of the anterior limb of the internal capsule (ALIC) was assessed via individual and normative tractography. RESULTS: Eighteen patients underwent laser anterior capsulotomy. Median follow-up was 6 months (range 3-51 months). Time occupied by obsessions improved immediately (median Y-BOCS item 1 score 4-1, p=0.002). Mean (±SD) decrease in Y-BOCS score at last follow-up was 46%±32% (16±11 points, p<0.0001). Sixty-one per cent of patients were responders. Seven patients (39%) exhibited transient postoperative apathy. One patient had an asymptomatic intracerebral haemorrhage. Reduction in Y-BOCS score was positively associated with ablation volume (p=0.006). Individual tractography demonstrated durable ALIC disconnection. Normative tractography revealed a dorsal-ventral gradient, with disconnection of orbitofrontal streamlines most strongly associated with a positive response (p<0.0001). CONCLUSIONS: Laser anterior capsulotomy resulted in immediate, marked improvement in OCD symptom severity. Larger lesions permit greater disconnection of prefrontal-subcortical pathways involved in OCD. The importance of greater disconnection is presumably related to variation in ALIC structure and the complex role of the PFC in OCD.

Surgical Outcomes and EEG Prognostic Factors After Stereotactic Laser Amygdalohippocampectomy for Mesial Temporal Lobe Epilepsy.

Objective: To assess the seizure outcomes of stereotactic laser amygdalohippocampectomy (SLAH) in consecutive patients with mesial temporal lobe epilepsy (mTLE) in a single center and identify scalp EEG and imaging factors in the presurgical evaluation that correlate with post-surgical seizure recurrence. Methods: We retrospectively reviewed the medical and EEG records of 30 patients with drug-resistant mTLE who underwent SLAH and had at least 1 year of follow-up. Surgical outcomes were classified using the Engel scale. Univariate hazard ratios were used to evaluate the risk factors associated with seizure recurrence after SLAH. Results: The overall Engel class I outcome after SLAH was 13/30 (43%), with a mean postoperative follow-up of 48.9 ± 17.6 months. Scalp EEG findings of interictal regional slow activity (IRSA) on the side of surgery (HR = 4.05, p = 0.005) and non-lateralizing or contra-lateralizing seizure onset (HR = 4.31, p = 0.006) were negatively correlated with postsurgical seizure freedom. Scalp EEG with either one of the above features strongly predicted seizure recurrence after surgery (HR = 7.13, p < 0.001) with 100% sensitivity and 71% specificity. Significance: Understanding the factors associated with good or poor surgical outcomes can help choose the best candidates for SLAH. Of the variables assessed, scalp EEG findings were the most clearly associated with seizure outcomes after SLAH.

Cognitive functioning of older adults prior to hematopoietic stem cell transplantation.

Hematopoietic cell transplantation is increasingly used in older adults with hematological malignancies. Younger adult patients who undergo HCT have shown to commonly present with cognitive impairment and depression prior to transplant; however, little research has been done to understand the cognitive and emotional functioning of older adults undergoing HCT. This study aimed to investigate the rate of cognitive impairment in a retrospective sample of older adult HCT candidates prior to transplant using a comprehensive battery. Ninety-three patients over the age of 60 completed a neuropsychology test battery that assessed standard domains of cognitive and emotional functioning. Impairment was defined as z-scores = < -1.5 on at least two tests or a z score = < -2.0 on at least one test. Results indicated that over 68% of patients were impaired with nearly a third of the sample showing impairment in verbal learning and memory and approximately one fifth showing impairments in aspects of executive function, processing speed, and visual learning. Ten percent of the patients endorsed symptoms indicative of a clinical level of depression. Medical comorbidities nor depression predicted cognitive impairment. These findings suggest that older adults candidates for HCT are at risk for cognitive impairment prior to transplant and thus cognition should be a consideration when developing treatment plans.

Comparison of cognitive profiles in spinocerebellar ataxia subtypes: a case series.

BACKGROUND: The spinocerebellar ataxias (SCA) are a heterogeneous group of progressive neurodegenerative disorders that are associated with diffuse cerebellar atrophy. While the physical symptoms of this condition have long been studied, more attention has been given to cognitive changes in recent years. We describe a case series of four adults with various genetically-confirmed subtypes of SCA. CASE PRESENTATION: Patients with SCA types 2, 3, and 6 presented with impaired cognitive profiles consistent with the existing literature while the reported patient with SCA-14 showed notable impairment inconsistent with the only published case controlled study. CONCLUSIONS: Comparisons were made between the four patients with a common pattern of slowed processing speed, poor memory retrieval, and reduced mental flexibility. Confrontation naming and consolidation-based memory were intact across all patients. These findings are discussed in light of the relevant literature on cerebellar cognitive affective syndrome.

Neurocognitive Functioning in Unoperated Adults with Chiari Malformation Type I.

OBJECTIVE: Adults with Chiari malformation type 1 (CM1) often report cognitive impairment. This cross-sectional study investigates the cognitive and emotional functioning of a sample of adults with CM1 who presented for neurosurgical evaluation prior to intervention. METHODS: A total of 36 participants (18 patients with CM1 and 18 healthy control subjects) completed a comprehensive neurocognitive battery of tests. RESULTS: Demographic variables (sex, age, handedness, and education) were not statistically significant between the groups. Measures of gross cognition (Mini-Mental State Examination and Repeatable Battery for the Assessment of Neuropsychological Status) were statistically significant between the groups. On a more focused assessment of neurocognitive abilities, the CM1 group performed significantly worse on measures of learning, memory, fluency, and figural copy. A high rate of clinical depression was seen in the CM1 group; however, this did not correlate with cognitive performance. CONCLUSIONS: The CM1 group displayed subtle learning, semantic fluency, and complex construction difficulties compared with healthy control subjects. Although not correlated with cognition, adults with CM1 are at high risk for clinical depression.

Prevalence of Psychiatric Diagnoses in Pediatric Chiari Malformation Type 1.

This cross-sectional study investigates the prevalence and risks for psychiatric diagnoses in a large cohort of children with Chiari malformation type 1 (CM1) presenting for neurosurgical evaluation. Children between the ages of 6 and 17 years who were evaluated and diagnosed with CM1 at a neurosurgery clinic were identified. Eighty-six participants were recruited for this study with an average age of 11 years. Parents of participants completed a pediatric medical history questionnaire and a semistructured interview regarding the child's psychiatric, developmental, medical, and family history. A review of medical records was completed to complement interview data. Elevated rates of psychiatric diagnoses, including attention deficit hyperactivity disorder (ADHD) (22.1%), anxiety (12.8%), and depression (10.5%), were identified in the study population when compared to published norms in the general population documented by the American Psychiatric Association in 2013. In addition, elevated rates of psychiatric diagnoses in first-degree relatives of study participants were also identified. A 2-step binary logistic regression analysis revealed that maternal complications during pregnancy (Wald = 6.52, p = 0.01) increased the risk of a psychiatric diagnosis 9-fold. Premature birth (Wald = 6.79, p = 0.01) also significantly predicted a psychiatric diagnosis amongst participants. The current findings suggest a high prevalence of psychiatric illness in children with CM1. Pregnancy complications were associated with a high risk of a psychiatric diagnosis. Early CNS developmental disturbance may explain this relationship. Prematurity only slightly improved the prediction model. Limitations and future directions are discussed, including the cross-sectional nature of the present study, possible self-selection bias, and the importance of future investigation of other causative and/or associative factors of CM1, such as cognitive, psychiatric, and medical influences on health status.

Stereotactic EEG-guided laser interstitial thermal therapy for mesial temporal lobe epilepsy.

OBJECTIVE: To determine the outcomes of combined stereo-electroencephalography-guided and MRI-guided stereotactic laser interstitial thermal therapy (LITT) in the treatment of patients with drug-resistant mesial temporal lobe epilepsy (mTLE). METHODS: We prospectively assessed the surgical and neuropsychological outcomes in 21 patients with medically refractory mTLE who underwent LITT at the University of Chicago Medical Center. We further compared the surgical outcomes in patients with and without mesial temporal sclerosis (MTS). RESULTS: Of the 21 patients, 19 (90%) underwent Invasive EEG study and 11 (52%) achieved freedom from disabling seizures with a mean duration of postoperative follow-up of 24±11 months after LITT. Eight (73%) of 11 patients with MTS achieved freedom from disabling seizures, whereas 3 (30 %) of 10 patients without MTS achieved freedom from disabling seizures. Patients with MTS were significantly more likely to become seizure-free, as compared with those without MTS (P=0.002). There was no significant difference in total ablation volume and the percentage of the ablated amygdalohippocampal complex between seizure-free and non-seizure-free patients. Presurgical and postsurgical neuropsychological assessments were obtained in 10 of 21 patients. While there was no group decline in any neuropsychological assessment, a significant postoperative decline in verbal memory and confrontational naming was observed in individual patients. CONCLUSIONS: MRI-guided LITT is a safe and effective alternative to selective amygdalohippocampectomy and anterior temporal lobectomy for mTLE with MTS. Nevertheless, its efficacy in those without MTS seems modest. Large multicentre and prospective studies are warranted to further determine the efficacy and safety of LITT.

Parent-Reported Executive Dysfunction in Children and Adolescents with Chiari Malformation Type 1.

BACKGROUND: Children with Chiari malformation type 1 (CM1) have increasingly presented to neurosurgery clinics. Limited research relating to the cognitive dysfunction experienced by this population has been completed. In adults, inhibition problems and executive dysfunction have been documented. METHODS: Seventy-seven parental reports of children with CM1 were included in the study. Parents completed questions on a scale rating daily executive functioning as well as reporting on common neurological symptoms. RESULTS: The sample consisted of 41 males and 36 females with a mean age of 133.57 ± 42.18 months. Thirty-eight subjects had had decompression surgery. The most common neurological symptoms included: headache (69%), a history of pain (31%) and gait disturbance (20%). One third of the sample demonstrated overall executive functioning impairment, with working memory elevations being most prevalent (44%). Depression, gender, age and decompression surgery were not related to executive dysfunction. CONCLUSIONS: The parental report of executive dysfunction in children with CM1 was higher than the standardized healthy sample. Metacognitive problems, especially working memory and initiation problems were most prevalent. A quick parental rating scale identifying children with executive dysfunction may be beneficial for neurosurgeons and assist with referrals for a more comprehensive neuropsychological assessment.

Standardized mini-mental state examination scores and verbal memory performance at a memory center: implications for cognitive screening.

Memory decline is often among the first signs heralding the emergence of mild cognitive impairment or dementia regardless of etiology. Despite its limited inclusion of memory screening, the Mini-Mental State Exam (MMSE) continues to be the most ubiquitous, first-line screening tool for dementia and cognitive decline. In response to well documented problems with the sensitivity of this instrument and the growing importance of cognitive screening, we assessed the utility of the MMSE as a screening tool among older adults presenting for evaluation at a memory clinic. The Standardized MMSE and a standardized verbal memory test - the Hopkins Verbal Learning Test-Revised (HVLT-R) - were administered to 304 consecutive referrals at a university-based outpatient memory clinic. Among patients scoring above 25 on the MMSE (n = 169), over half exhibited at least moderate memory impairment (HVLT-R delayed recall z ≤ -2.0) and more than 25% showed severe impairment (delayed recall z ≤ -3.0). Perhaps even more striking was that among those who achieved perfect (30/30) or near perfect (29/30) scores on the MMSE (n = 70), 43% displayed moderate to severe memory impairment. Although newer screening measures have shown improved sensitivity, more in-depth memory testing appears to be a vital component of successful screening and early detection.

The effects of long-term interferon-beta-1b treatment on cognitive functioning in multiple sclerosis: a 16-year longitudinal study.

BACKGROUND: Multiple sclerosis (MS) is a progressive disease of the central nervous system that affects cognition. Short-term treatment with interferon-beta-1b (IFN-b-1b) has been shown to have beneficial effects on cognition. OBJECTIVE: The objective of this paper is to evaluate the effects of IFN-b-1b on cognitive functioning in patients with MS over the course of 16 years. METHODS: Sixteen subjects with relapsing-remitting MS participated in the study. Nine of these subjects received IFN-b-1b, while seven received placebo treatment in the pivotal MS trial. After five years, all subjects were switched to IFN-b-1b treatment. At two and four years into the study, all subjects underwent a brief neuropsychological test battery, magnetic resonance imaging (MRI), and neurologic ratings; measures were repeated at 16 years. RESULTS: Across the total cohort, cognitive functioning remained relatively stable over the course of 16 years. The placebo/IFN-b-b group exhibited increased visual memory performance relative to the IFN-b-1b treatment group, but had a greater decline in verbal memory. Initial MRI lesion load demonstrated a significant, negative correlation with overall cognitive performance at 16 years (p = 0.00). CONCLUSION: We conclude that IFN-b-1b has beneficial effects on long-term cognition outcomes in MS.

Parent ratings of executive functioning in children with shunted hydrocephalus.

OBJECTIVES: The present study examined the executive functioning of a group of children with a history of communicating hydrocephalus and how their level of functioning was correlated with parent ratings of executive functioning. METHODS: The study examined the executive functioning of 39 shunted children with a history of hydrocephalus and 20 healthy peers. Additionally, parents of both groups of children completed the Behavior Rating Inventory of Executive Function (BRIEF) to assess the parents' perceptions of their children's executive functioning. Finally, the study investigated the relationship between the shunted hydrocephalus children's executive functioning and the parent ratings of their executive functioning. RESULTS: Overall, the children with a history of shunted hydrocephalus displayed more executive dysfunction than their healthy peers. These children were rated by their parents as having more executive dysfunction than their healthy peers and displaying working memory, initiation, mental flexibility and self-monitoring difficulties, which appear to increase with age among the shunted hydrocephalus group. While parent ratings as measured by the BRIEF indices did not correlate with all executive tasks within the shunted hydrocephalus group, the cognitive tests assessing mental flexibility may be sensitive to the problems noted by parents at home. CONCLUSIONS: The children with a history of shunted hydrocephalus displayed executive functioning deficits on formal examination. The parents of children with a history of shunted hydrocephalus report ongoing executive difficulties which may increase with age.

Cognitive effects of androgen deprivation therapy in an older cohort of men with prostate cancer.

OBJECTIVE: To determine the baseline prevalence of cognitive impairment in older men treated with ADT and to assess changes in cognitive performance over time. METHODS AND RESULTS: Thirty-two patients (median age of 71 years, range 51-87) were administrated an extensive neuropsychological testing battery prior to ADT initiation, with 21 (65%) completing post-treatment evaluations 6 months later. At baseline, 45% scored >1.5 standard deviations below the mean on > or = 2 neuropsychological measures. Using standardized inferential statistics, no change in cognition was documented following treatment. The Reliable Change Index revealed that, on a case-by-case basis, 38% demonstrated a decline in measures of executive functioning and 48% showed improvement on measures of visuospatial abilities. Within exploratory analyses, patients who scored below expectation at baseline displayed no change in cognition, while patients with average or better scores at baseline displayed improvements in visuospatial planning and timed tests of phonemic fluency. CONCLUSIONS: We found a high prevalence of lower than expected cognitive performance among a sample of patients just starting ADT for prostate cancer. Assessment of baseline cognitive function should be taken into account for future research and to inform clinical management.

WITHDRAWN: Cognitive effects of androgen deprivation therapy in an older cohort of men with prostrate cancer.

This article has been withdrawn from Critical Reviews in Oncology/Hematology. With the permission of the authors, it has been published in Volume1, issue 1 of the Journal of Geriatric Oncology (www.geriatriconcology.net). The full Elsevier Policy on Article Withdrawal can be found at http://www.elsevier.com/locate/withdrawalpolicy.