Neuropsychological Assessment in a Case of Adult-Onset Hemophagocytic Lymphohistiocytosis (HLH)

We present a case of an individual diagnosed with hemophagocytic lymphohistiocytosis (HLH), an extremely rare and commonly fatal disorder characterized by rapid dysregulation of immune system processes. Typical age of onset is in childhood, with adult-onset occurring less frequently. The pathophysiology of this condition is characterized by a hyperinflammatory response with infiltration of visceral organs, lymph nodes, bone marrow, and the central nervous system. The clinical presentation has been documented in the extant medical literature. However, there appear to be no published reports of neuropsychological functioning in HLH patients. The patient we present here is a 28-year-old woman with 16 years of education who developed HLH subsequent to systemic lupus erythematosus flare-up. She was initially comatose for 3 weeks. Acute MRI reported multiple subcortical abnormalities, including the brainstem. The patient underwent chemotherapy, immunosuppresant, and steroid treatments. She underwent a neuropsychological evaluation at 2.5 and 7 months post initial presentation. Preliminary neuropsychological evaluation found impairments in motor abilities and aspects of executive functions. Subsequent evaluation showed improved executive function and relative sparing of higher-order cognitive abilities, but continued impairment on motor tests. To our knowledge this is the first study to report neuropsychological data for an adult diagnosed with HLH.     

The Neuropsychological Profile of Infantile Duchenne Muscular Dystrophy

It has been shown that children with Duchenne muscular dystrophy (DMD) exhibit specific cognitive deficits. However, the neuropsychological profile has not yet been fully characterized. In order to control for the contribution of motor impairments as a confounding variable that is usually present when assessing children with muscular pathologies, we compared children with DMD to a group of children with an autoimmune pathology that does not entail either brain or cognitive dysfunction but does imply motor impairment: juvenile rheumatoid arthritis (JRA). An extensive neuropsychological evaluation was administered, including intelligence, perception, language, memory and learning, attention, executive function, praxis and reasoning. As the main result, in children with DMD we found significantly lower performances in verbal IQ, verbal short-term memory and phonological abilities, as well as in praxis and executive functioning domains. A wide range of cognitive domains, including verbal abilities, executive functioning, and praxis, must be taken into account when assessing neuropsychological functioning in children with DMD. In particular, subtle executive function impairment could be considered as a subclinical marker of cognitive impairment in developmental disorders.     

The neuropsychological profile of infantile Duchenne muscular dystrophy

It has been shown that children with Duchenne muscular dystrophy (DMD) exhibit specific cognitive deficits. However, the neuropsychological profile has not yet been fully characterized. In order to control for the contribution of motor impairments as a confounding variable that is usually present when assessing children with muscular pathologies, we compared children with DMD to a group of children with an autoimmune pathology that does not entail either brain or cognitive dysfunction but does imply motor impairment: juvenile rheumatoid arthritis (JRA). An extensive neuropsychological evaluation was administered, including intelligence, perception, language, memory and learning, attention, executive function, praxis and reasoning. As the main result, in children with DMD we found significantly lower performances in verbal IQ, verbal short-term memory and phonological abilities, as well as in praxis and executive functioning domains. A wide range of cognitive domains, including verbal abilities, executive functioning, and praxis, must be taken into account when assessing neuropsychological functioning in children with DMD. In particular, subtle executive function impairment could be considered as a subclinical marker of cognitive impairment in developmental disorders.     

Neuropsychological Functioning in a Young Adult Case of Schizencephaly

Schizencephaly is a rare neuromigrational/organizational disorder characterized by the development of cerebral clefts, which are typically associated with neurological sequelae including seizures, motor disturbances, and cognitive dysfunction. Although there are multiple case reports of schizencephaly and associated neurological sequelae, primarily in children, the literature regarding neuropsychological manifestations of schizencephaly is limited. This article reviews the case of a woman diagnosed with bilateral schizencephaly at age 29. Neuropsychological testing revealed intact intelligence and memory functioning. However, impairments were noted in attention, executive functioning, expressive language skills, visual-spatial abilities, and bilateral manual motor skills, all of which were adversely impacting her functional abilities (e.g., ability to be gainfully employed). Given the potential variability in deficits associated with schizencephaly, this case demonstrates the utility of neuropsychological evaluation for understanding cognitive and functional consequences of bilateral schizencephaly.     

The fragile X premutation presenting as essential tremor

CONTEXT: The fragile X premutation has recently been reported to be associated with a neurodegenerative syndrome, chiefly characterized by intention tremor, gait ataxia, and executive cognitive deficits in men older than 50 years. Essential tremor is a frequent cause of tremor in elderly patients and in some cases is associated with impaired tandem gait and cognitive deficits. OBJECTIVE: To describe 2 fragile X carriers whose clinical presentation mimicked essential tremor. DESIGN: The 2 patients described herein underwent neurologic examinations by experienced movement disorders neurologists, magnetic resonance imaging, and fragile X gene, messenger RNA, and protein analyses. One underwent detailed neuropsychological testing. SETTING: Patients were studied at 2 large university movement disorders clinics. PATIENTS: Both patients were white men older than 50 years who had been diagnosed as having essential tremor and then found to be fragile X carriers. RESULTS: Besides disabling intention tremor, the 2 patients had impaired tandem, generalized brain atrophy, and unusual bilateral T2 middle cerebellar hyperintensities on magnetic resonance imaging. The patient who underwent neuropsychological testing had frontal executive deficits. Both patients had elevated fragile X mental retardation gene 1 messenger RNA and reduced fragile X mental retardation 1 protein levels. CONCLUSION: The fragile X carrier state may underlie the clinical findings in some older men diagnosed as having essential tremor.     

Neuropsychological function in obsessive-compulsive disorder

Obsessive-compulsive disorder (OCD) is a chronic disease characterized by repetitive, unwanted intrusive thoughts and ritualistic behaviors. Studies of neuropsychological functions in OCD have documented deficits in several cognitive domains, particularly with regard to visuospatial abilities, executive functioning, and motor speed. The objective of the present study was to investigate systematically the cognitive functioning of OCD patients who were free of medication and comorbid psychiatric disorders. In the present study, 72 OCD patients were compared with 54 healthy controls on their performance in a comprehensive neuropsychological battery. The Yale-Brown Obsessive Compulsive Scale and the Hamilton Depression Rating Scale were administered to the patients, and a semistructured interview form was used to evaluate the demographic features of the patients and control subjects. Overall, widespread statistically significant differences were found in tests related to verbal memory, global attention and psychomotor speed, and visuospatial and executive functions indicating a poorer performance of the OCD group. A closer scrutiny of these results suggests that the OCD group has difficulty in using an effective learning strategy that might be partly explained by their insufficient mental flexibility and somewhat poor planning abilities.     

Dual-task clinical and functional MRI correlates in Parkinson's disease with postural instability and gait disorders

BackgroundDual-task is a challenge for Parkinson's disease patients with postural instability and gait disorders (PD-PIGD).ObjectiveThis study investigated clinical, cognitive and functional brain correlates of dual-task deficits in PD-PIGD patients using quantitative gait analysis, neuropsychological evaluations and functional MRI (fMRI).MethodsTwenty-three PD-PIGD patients performed a clinical assessment of gait/balance abilities. Single and dual-task Timed-Up-and-Go tests were monitored using an optoelectronic system to study turning velocity. Patients underwent executive-attentive function evaluation and two fMRI tasks: motor-task (foot anti-phase movements), and dual-task (foot anti-phase movements while counting backwards by threes starting from 100). Twenty-three healthy subjects underwent neuropsychological and fMRI assessments.ResultsDual-task in PD-PIGD patients resulted in worse gait performance, particularly during turning. Performing the dual-task relative to the motor-fMRI task, healthy subjects showed widespread increased recruitment of sensorimotor, cognitive and cerebellar areas and reduced activity of inferior frontal and supramarginal gyri, while PD-PIGD patients showed increased recruitment of inferior frontal gyrus and supplementary motor area and reduced activity of primary motor, supramarginal and caudate areas. Dual-task gait alterations in patients correlated with balance and executive deficits and with altered dual-task fMRI brain activity of frontal areas.ConclusionsThis study suggested the correlation between dual-task gait difficulties, postural instability and executive dysfunction in PD-PIGD patients. FMRI results suggest that an optimized recruitment of motor and cognitive networks is associated with a better dual-task performance in PD-PIGD. Future studies should evaluate the effect of specific gait/balance and dual-task trainings to improve gait parameters and optimize brain functional activity during dual-tasks.     

Multiple system atrophy with early cognitive deficits: A case report

We present the case of a patient with multiple system atrophy with predominant cerebellar ataxia (MSA-C) in the early stage of the disease, who was assessed using a comprehensive neuropsychological test battery. Many studies have found cognitive deficits in MSA patients assessed after 2–3 years, but not in the first stages of the disease. The aim of this paper is to stress the importance of a complete neuropsychological assessment, even at the initial stage of the disease, when instrumental examinations are not able to show cortical involvement and daily life activities have not been affected. The neuropsychological tests examined general cognition, verbal and visual memory, visuospatial and constructional ability, language, executive function, depression and functional autonomy. Results showed cognitive deficits in executive functions, above all in the control and inhibition of automatic response, planning and reasoning abilities, memory and visuoconstructional functions. However, these problems did not affect the patient’s autonomy in everyday life. MRI scan showed the involvement of the cerebellum and the fibers of the pons and raphe, with normal cerebral ventricles and sulci. The cognitive deficits in our patient could be explained by a disruption in cerebrocerebellum connections between the frontal areas and the cerebellar structures. These results show that a more comprehensive cognitive evaluation is necessary to detect early the onset of neuropsychological deficits, also in order to begin in time adequate rehabilitation programs.     

Severe Episodic Memory Impairment in a Patient With Clinical Features Compatible With Corticobasal Degeneration

Corticobasal degeneration (CBD) is a progressive neurodegenerative disorder characterized by asymmetric parkinsonism associated with apraxia, cortical sensory loss, and alien-limb phenomenon. Neuropsychological testing in patients with CBD typically shows deficits in executive functions, praxis, language, and visuospatial functioning, but not in memory. We report a CBD patient with severely impaired memory function but relatively mild motor symptoms. Detailed neuropsychological assessment showed significant verbal and visual memory deficits accompanied by frontal executive dysfunctions. Our observations indicate that CBD can in rare cases present with severe episodic memory impairment associated with frontal executive dysfunctions in the early stage of illness.     

Impairment in visual-spatial function in catatonia: a neuropsychological investigation.

Catatonia is a psychomotor syndrome with motor and behavioral abnormalities which may be due to alterations in fronto-parietal cortical function. We therefore investigated neuropsychological tasks (attention, executive, visual-spatial, working memory) associated with frontal and parietal cortical function. Thirteen catatonic patients, diagnosed as catatonic according to criteria by Rosebush and Bush, were compared with 13 psychiatric non-catatonic controls (matched with regard to underlying psychiatric diagnosis, age, sex, and medication), and 13 age- and sex-matched healthy controls. Catatonics showed significantly poorer performances and different neuropsychological intercorrelation patterns in visual spatial object perception (VOSPobject) than psychiatric and healthy controls. In addition, we found significant correlations between catatonic symptoms, visual-spatial abilities, and attentional measures (i.e., d2, CWI). Catatonia was characterized by specific visual-spatial deficits which are related to attentional abilities and right parietal cortical function. The data suggest attentional-motor and fronto-parietal dysfunction in catatonia, a conclusion which should be considered as preliminary, however, due to the small sample size.     

Memory lost, memory regained: neuropsychological findings and neuroimaging in two cases of paraneoplastic limbic encephalitis with radically different outcomes

OBJECTIVE: To report two cases of paraneoplastic limbic encephalitis (PNLE) with similar clinical presentation, but dramatically different outcome and to highlight the role of neuropsychological and radiological evaluation in PNLE. METHODS: Both patients underwent an extensive battery of neuropsychological tests designed to document general intellectual function, anterograde verbal and visual memory, naming, knowledge and executive ability. In addition, structural (CT and MRI) and functional (HMPAO-SPECT) brain scans were performed. RESULTS: Both patients presented with fairly sudden onset of profound and persistent memory loss in the absence of other neurological symptoms. Their subsequently diagnosed small cell lung cancer was treated with a combination of radiotherapy and chemotherapy, leading to remission of the tumour. The memory of patient 1 recovered fully and he died from an unrelated cause 1 year later; neuropsychological testing showed a severe, but isolated, anterograde amnesia, brain MRI was normal and HMPAO-SPECT showed left medial temporal hypoperfusion. Patient 2 remained densely amnesic despite regression of her lung tumour; neuropsychological testing disclosed both anterograde and extensive retrograde amnesia together with more generalised cognitive deficits including anomia and executive impairments, MRI showed gross atrophy of the hippocampus and amygdala bilaterally, and HMPAO-SPECT showed pronounced frontal and temporal hypoperfusion. CONCLUSION: Complete remission from PNLE may occur and seems to be associated with pure anterograde amnesia without evidence of structural hippocampal damage in MRI. By contrast, cognitive deficits beyond severe anterograde amnesia and evidence of destructive medial temporal lobe pathology on MRI seem to be poor prognostic features.     

Diagnostic difficulties due to atypical symptoms in normal pressure hydrocephalus. A case report

This paper presents a case of a female patient with unusual symptoms of diagnosed hydrocephalus. Symptoms demonstrated by the patient were initially diagnosed as immature personality, after that she was diagnosed with reactive depressive disorders. For those reasons she was treated for over 20 years in different psychiatric outpatient clinics and psychiatric hospitals. She was treated pharmacologically with different medications: antidepressants, neuroleptics etc. She also participated periodically in individual and group psychotherapy. Computed tomography performed after the loss of consciousness with significant motor deficits revealed relevant dilation of the cerebral ventricular system. The neuropsychological examination revealed disturbances in emotional-motivation area and cognitive deficits. Those disorders caused significant problems in social and professional activities. After completing the diagnosing process the patient was diagnosed with arrested hydrocephalus. Results of clinical examinations suggested that at this stage of the disease there are no indications for shunt implantation. Probably earlier diagnosis could bring a chance of successful neurosurgical intervention and definitely more efficient therapy.     

Cognitive impairment in a 65-year-old male with the fragile X-associated tremor-ataxia syndrome (FXTAS).

OBJECTIVE: This is the first case report of a comprehensive neuropsychologic examination of an older man with the fragile X-associated tremor-ataxia syndrome (FXTAS). BACKGROUND: FXTAS, a newly identified phenotype affecting older male carriers of the fragile X premutation allele, is a progressive disorder marked by gait ataxia, action tremor, peripheral neuropathy, executive cognitive deficits, generalized brain atrophy, and neuronal and astrocytic intranuclear inclusion bodies throughout the brain. The patient previously had undergone neurologic evaluation, molecular analysis, and magnetic resonance imaging. METHOD: The patient was administered a neuropsychologic examination, assessing motor and somatosensory functioning, visual and spatial functioning, speech and language, attention, executive abilities, learning and memory, and reasoning. RESULTS: The patient showed a pattern of cognitive impairment characterized by essentially normal speech and language, moderately impaired control of attention, and moderate to severe deficits in working memory, executive functioning, and both declarative and procedural learning. Visual and spatial abilities were relatively unimpaired, and verbal reasoning was only mildly deficient. CONCLUSIONS: The findings suggest that a cognitive disorder, with especially marked executive cognitive function and memory deficits, accompanies FXTAS. The findings in FXTAS are compared with those in several other neurodegenerative disorders.     

Cognitive dimensions in first-episode schizophrenia spectrum disorders

BACKGROUND: The severity and pattern of cognitive deficits in epidemiological cohorts of patients with first-episode schizophrenia spectrum disorders still remains unclear. We aimed to characterize the basic cognitive functioning of a representative sample of patients with a first-episode schizophrenia spectrum disorders. METHOD: One hundred thirty-one patients experiencing first-episode psychosis and 28 healthy volunteers were administered a comprehensive neuropsychological evaluation. To reduce the number of cognitive test measures into meaningful cognitive dimensions, before analyzing differences between patient and healthy volunteer samples, exploratory factor analysis was carried out on data collected in patients group. The method of extraction was Principal Components Analysis with oblique rotation. RESULTS: An eight-factor model including verbal learning/memory, verbal comprehensive abilities, speed of processing/executive functioning, motor dexterity, motor speed, sustained attention, and impulsivity emerged. A significant below average performance in all cognitive dimensions, except impulsivity, was found. Patient's performance in speed of processing/executive functioning, motor dexterity and sustained attention dimensions exceeded one standard deviation below healthy comparison subjects. CONCLUSIONS: At early stages of the illness, patients display a marked impairment in several functionally relevant cognitive domains.     

MR imaging and cognitive correlates of relapsing–remitting multiple sclerosis patients with cerebellar symptoms

Multiple sclerosis (MS) is a demyelinating disease affecting the central nervous system, frequently associated with cognitive impairments. Damages of the cerebellum are very common features of patients with MS, although the impact of this clinical factor is generally neglected. Recent evidence from our group demonstrated that MS patients with cerebellar damages are characterized by selective cognitive dysfunctions related to attention and language abilities. Here, we aimed at investigating the presence of neuroanatomical abnormalities in relapsing–remitting MS patients with (RR-MSc) and without (RR-MSnc) cerebellar signs. Twelve RR-MSc patients, 14 demographically, clinically, and radiologically, matched RR-MSnc patients and 20 controls were investigated. All patients underwent neuropsychological assessment. After refilling of FLAIR lesions on the 3D T1-weighted images, VBM was performed using SPM8 and DARTEL. A correlation analysis was performed between VBM results and neuropsychological variables characterizing RR-MSc patients. Despite a similar clinical status, RR-MSc patients were characterized by more severe cognitive damages in attention and language domains with respect to RR-MSnc and controls. With respect to controls, RR-MSnc patients were characterized by a specific atrophy of the bilateral thalami that became more widespread (including motor cortex) in the RR-MSc group (FWE < 0.05). However, consistent with their well-defined neuropsychological deficits, RR-MSc group showed atrophies in the prefrontal and temporal cortical areas when directly compared with RR-MSnc group. Our results demonstrated that RR-MS patients having cerebellar signs were characterized by a distinct neuroanatomical profile, mainly involving cortical regions underpinning executive functions and verbal fluency.     

Executive and emotional dysfunction in Machado-Joseph disease.

Machado-Joseph disease (MJD) is an autosomal dominant spinocerebellar ataxia. Few studies have examined the neuropsychological and neurobehavioral profiles of patients with MJD. In this study, six individuals with MJD were given a battery of neuropsychological tests. Relative impairments on timed verbal attention tasks and verbal fluency (Stroop, Oral Symbol Digit Modalities, and Controlled Oral Word Association Test) were found. Other executive impairments also were seen on the Wisconsin Card Sorting Test, independent of motor dysfunction severity. Moderate- to severe levels of depressive symptoms were endorsed by four of the six patients, and caregivers observed increased apathy in the patients. Impaired executive and emotional functioning in MJD does not appear to be related to ataxia severity. These patients did not meet the criteria for dementia. General cognitive abilities, language, list learning, story recall, and untimed tasks of attention were within normal limits. Impaired executive abilities and emotional functioning in MJD patients is consistent with disruption of frontal-subcortical systems.     

Determinants of delayed diagnosis in Parkinson’s disease

The early and accurate diagnosis of Parkinson’s disease (PD) is the first step towards optimal patient management. The aim of this study was to investigate the major determinants of delayed diagnosis in PD. We recruited a population-representative cohort of 239 newly-diagnosed PD patients who underwent clinical and neuropsychological evaluation. Non-parametric methods were used to define the factors associated with diagnostic delay. The median time from motor symptom onset to primary care physician (PCP) presentation was considerably longer than the time from PCP presentation to PD diagnosis (11 vs. 1 months). Male sex and presenting motor phenotype were independently associated with delayed PCP presentation on Cox regression analysis. Patients presenting with gait disturbance experienced the longest delay, whilst those presenting with tremor had the shortest. In summary, male sex and presenting motor phenotype are key determinants of delayed diagnosis in PD.     

Neuropsychological Profile in Children with Posterior Fossa Tumors with or Without Postoperative Cerebellar Mutism Syndrome (CMS)

Cerebellar mutism syndrome (CMS) is a common surgical sequela in children following posterior fossa tumor (PFT) resection. Here, we analyze the neuropsychological features associated with PFT in children, focusing particularly on the differential profiles associated with the presence or absence of CMS after surgery. We further examine the effect of post-resection treatments, tumor type, and presence/absence of hydrocephalus on surgical outcome. Thirty-six patients diagnosed with PFT (19 with and 17 without CMS) and 34 age- and gender-matched healthy controls (HCs) were recruited. A comprehensive neuropsychological evaluation was conducted in all patients postoperatively and in HCs, including an assessment of general cognitive ability, motor skills, perception, language, memory, attention, executive functions, and academic competence. CMS was found to be a clinical marker of lower neuropsychological profile scores across all cognitive domains except auditory-verbal processing and visual memory tasks. PFT patients not presenting CMS exhibited milder impairment in intellectual functioning, motor tasks, reasoning, language, verbal learning and recall, attention, cognitive executive functions, and academic competence. High-grade tumors were associated with slower processing speed and verbal delayed recall as well as alterations in selective and sustained attention. Hydrocephalus was detrimental to motor functioning and nonverbal reasoning. Patients who had undergone surgery, chemotherapy, and radiotherapy presented impaired processing speed, verbal learning, and reading. In addition to the deleterious effects of PFT, post-resection PFT treatments have a negative cognitive impact. These undesired consequences and the associated tumor-related damage can be assessed using standardized, long-term neuropsychological evaluation when planning rehabilitation.     

Neuropsychological assessment of executive functions

This article discusses the neuropsychological assessment of executive functions with respect to relevant clinical issues. Although neural mechanisms of executive dysfunction are postulated to involve the frontal lobes, the vital contribution of nonfrontal brain regions to executive abilities cannot be underestimated. A comprehensive neuropsychological testing approach, supplemented with keen observation of behavior outside the formal testing setting, is imperative in the determination of executive dysfunction. The development of clinically useful psychometric instruments in assessing executive functions is central to the evaluation of cognitive capabilities of individuals with a wide range of neuropsychiatric disorders. The clinician must also be aware of the limitations of "frontal" tests and take these limitations into consideration when addressing issues of assessment.     

Probable Alzheimer's disease patients presenting as "focal temporal lobe dysfunction" show a slow rate of cognitive decline

Several authors have recently shown that anterograde amnesia is often associated with semantic memory impairment in amnesic MCI patients. Similarly, after the MCI condition, some patients who convert to Alzheimer's disease (AD) show the classic onset (cAD) characterized by the impairment of memory and executive functions, whereas other AD patients show isolated defects of episodic and semantic memory without deficits in other cognitive domains. The latter have been considered an AD variant characterized by 'focal Temporal Lobe Dysfunction' (TLD). The aim of the present study was to assess the differences in disease progression between cAD and TLD. For this purpose a continuous series of newly diagnosed probable AD patients presenting as cAD (n = 30) and TLD (n = 25), matched for severity, and 65 healthy controls underwent a comprehensive neuropsychological evaluation at baseline; TLD and cAD were re-evaluated at a 24-month follow-up. At follow-up, TLD patients showed no significant worsening of cognitive functions, whereas cAD subjects displayed a significant worsening in all explored cognitive domains. In conclusion, our results confirm that probable AD presenting as TLD represents a specific onset of AD characterized by a slower rate of progression.