I can't count, but I can beat you playing cards: a case report on autoimmune encephalitis.

BACKGROUND: Autoimmune encephalitis (AE) is a rare inflammatory disorder characterized by important psychiatric and neurologic symptoms. The literature documents high rates of neuropsychological dysfunction in N-methyl D-aspartate-receptor (NMDAr) encephalitis but papers don't consider specifically calculation disturbances between the long-term deficits, although deficits in executive control and episodic memory were less likely to resolve. CASE REPORT: Here we present a severe case of NMDAr encephalitis in a young patient without a relevant past medical history. Upon first examination he presented psycho-motor slowdown, speech disorders, severe cognitive deficits in all areas: concentration, attention, memory, language, dual task functions, increased latency in responses, severe dyscalculia. Upon first evaluation, the young patient underwent a battery of neuropsychological tests and he showed a dysexecutive syndrome with performances significantly low for age and education. Our patient hence underwent 1 month of intensive cognitive rehabilitation. After the rehabilitation treatment, he presented an amelioration in all domains except calculations. CONCLUSIONS: In our patient the calculation disorder has proved to be the most relevant problem and the most difficult to treat. Clinicians should consider a careful approach to determine the prognosis of this syndrome because of the wide range of deficits, the need of prolonged treatment and the rate of long-term sequelae.

Electromyographic assessment of paratonia.

Many years after its initial description, paratonia remains a poorly understood concept. It is described as the inability to relax muscles during muscle tone assessment with the subject involuntary facilitating or opposing the examiner. Although related to cognitive impairment and frontal lobe function, the underlying mechanisms have not been clarified. Moreover, criteria to distinguish oppositional paratonia from parkinsonian rigidity or spasticity are not yet available. Paratonia is very frequently encountered in clinical practice and only semi-quantitative rating scales are available. The purpose of this study is to assess the feasibility of a quantitative measure of paratonia using surface electromyography. Paratonia was elicited by performing consecutive metronome-synchronized continuous and discontinuous elbow movements in a group of paratonic patients with cognitive impairment. Goniometric and electromyographic recordings were performed on biceps and triceps brachii muscles. Facilitatory (mitgehen) and oppositional (gegenhalten) paratonia could be recorded on both muscles. After normalization with voluntary maximal contraction, biceps showed higher paratonia than triceps. Facilitatory paratonia was higher than oppositional on the biceps. Movement repetition induced increased paratonic burst amplitude only when flexion and extension movements were performed continuously. Both facilitatory and oppositional paratonia increased with movement repetition. Only oppositional paratonia increased following faster movements. This is the first study providing a quantitative and objective characterization of paratonia using electromyography. Unlike parkinsonian rigidity, oppositional paratonia increases with velocity and with consecutive movement repetition. Like spasticity, oppositional paratonia is velocity-dependent, but different from spasticity, it increases during movement repetition instead of decreasing. A quantitative measure of paratonia could help better understanding its pathophysiology and could be used for research purposes on cognitive impairment.

Agomelatine Improves Apathy in Frontotemporal Dementia.

BACKGROUND/AIMS: Apathy is the most common initial symptom of frontotemporal dementia (FTD) and has been linked to frontal-subcortical dopaminergic system dysfunction. No pharmacological therapy has been approved for the treatment of apathy, but, on the basis of its physiopathological mechanism, we suspected that increasing prefrontal dopaminergic innervation could improve this disabling symptom. METHODS: We evaluated a group of 24 nondepressed patients with a diagnosis of the behavioral variant of FTD, in order to determine the effectiveness on apathy of agomelatine, an antidepressant with MT1 and MT2 receptor agonism and 5-HT2C receptor antagonism; the latter leads to an increase in prefrontal dopaminergic and noradrenergic tone. To try to tease out the effects of 5-HT2C antagonism on apathy, patients were randomized, using a cross-over design, to receive either agomelatine 50 mg/day or sustained release melatonin 10 mg/day for 10 weeks in a double-blind procedure. At the end of the follow-up period, subjects receiving melatonin switched to agomelatine for the following 10 weeks. RESULTS: Agomelatine, but not melatonin, was associated with a significant reduction of apathy in FTD subjects and of caregiver distress due to patients' apathy. The switch from melatonin to agomelatine was associated with a reduction in apathetic behavior. Agomelatine was well-tolerated by all enrolled subjects. CONCLUSIONS: Our data, albeit preliminary, suggest that agomelatine could represent a novel useful approach to the treatment of apathy in FTD patients.

Souvenaid reduces behavioral deficits and improves social cognition skills in frontotemporal dementia: a proof-of-concept study.

BACKGROUND: Souvenaid™ is a nutraceutical compound thought to positively enhance synaptic function. In line with this mechanism of action, Souvenaid™ has been shown to improve cognitive function in subjects with mild Alzheimer's disease in randomized clinical trials. To date, however, the potential of Souvenaid™ to improve cognitive functioning in subjects with other neurodegenerative conditions also characterized by synaptic loss has not been explored. OBJECTIVE: To evaluate the impact of Souvenaid™ on executive functions, social cognition and behavioral disturbances in subjects with the behavioral variant of frontotemporal dementia (bv-FTD). METHODS: Twenty-six subjects with bv-FTD were enrolled in the study and randomized to Souvenaid™ (125 ml/day) or placebo groups. After 12 weeks, subjects were switched between the two groups. All subjects, blinded to treatment, underwent clinical and cognitive evaluations at enrollment, after 12 weeks and after 24 weeks. RESULTS: Treatment with Souvenaid™ was associated with a significant reduction of behavioral symptoms and an increase in Theory of Mind skills compared to placebo, which both returned to baseline when Souvenaid™ was discontinued. Souvenaid™ did not have an effect on executive functions. CONCLUSIONS: Our results provide evidence of the potential of Souvenaid™ therapy for the treatment of behavioral disturbances and social cognition skills in FTD.

Cognitive impairment assessment through handwriting (COGITAT) score: a novel tool that predicts cognitive state from handwriting for forensic and clinical applications.

Introduction: Handwriting deteriorates proportionally to the writer's cognitive state. Such knowledge is of special importance in the case of a contested will, where dementia of the testator is claimed, but medical records are often insufficient to decide what the testator's cognitive state really was. By contrast, if the will is handwritten, handwriting analysis allows us to gauge the testator's cognitive state at the precise moment when he/she was writing the will. However, quantitative methods are needed to precisely evaluate whether the writer's cognitive state was normal or not. We aim to provide a test that quantifies handwriting deterioration to gauge a writer's cognitive state. Methods: We consecutively enrolled patients who came for the evaluation of cognitive impairment at the Outpatient Clinic for Cognitive Impairment of the Department of Neuroscience, Rehabilitation, Ophthalmology, Genetics and Maternal and Child Sciences (DINOGMI) of the University of Genoa, Italy. Additionally, we enrolled their caregivers. We asked them to write a short text by hand, and we administered the Mini Mental State Examination (MMSE). Then, we investigated which handwriting parameters correlated with cognitive state as gauged by the MMSE. Results: Our study found that a single score, which we called the COGnitive Impairment Through hAndwriTing (COGITAT) score, reliably allows us to predict the writer's cognitive state. Conclusion: The COGITAT score may be a valuable tool to gage the cognitive state of the author of a manuscript. This score may be especially useful in contested handwritten wills, where clinical examination of the writer is precluded.

Isolated theory of mind deficits and risk for frontotemporal dementia: a longitudinal pilot study.

OBJECTIVE: Recent data suggest that theory of mind (ToM) deficits represent an early symptom of the behavioural variant of frontotemporal dementia (bvFTD). However, longitudinal data on the natural history of subjects presenting with isolated ToM deficits are lacking. The aim of the study was to verify if isolated ToM deficits represent an at-risk state for prefrontal dysfunction and bvFTD. METHODS: A population of healthy subjects (n=4150, age range: 50-60 years) completed a clinical and neuropsychological evaluation including the Reading the Mind in the Eyes Test (RMET), a widely used ToM task. From this group, we recruited a low-RMET group (n=83) including subjects with RMET scores lower than 2 SDs but an otherwise normal neuropsychological evaluation and a control group. All subjects underwent evaluation at baseline and after 2 years. RESULTS: Subjects in the low-RMET group showed decline in prefrontal functions at follow-up. Moreover, at follow-up 12 subjects in the low-RMET group presented with findings suggestive of bvFTD. Neuropsychological performance was stable in the control group. CONCLUSIONS: Our data suggest that isolated ToM deficits could represent an at-risk situation for the development of future prefrontal dysfunction and bvFTD. ToM evaluation should be included in neuropsychological protocols aimed to evaluate the early phases of dementia.

Transient global amnesia after breathing hyperoxic mixtures in otherwise regular dives.

The diagnosis of decompression sickness may be difficult, particularly when patients present with atypical clinical manifestations after dives going on uneventfully and with full adherence to safety parameters. The case reports involve two divers who presented with transient global amnesia (TGA) immediately after surfacing from otherwise regular dives during which they had been breathing hyperoxic mixtures (Nitrox). A wide spectrum of symptoms of neural dysfunction following hyperoxic mixtures have been reported, including cases of memory impairment related to previous generalized convulsions. After a review of the literature, however, we found no previous reports of TGA, which is very unlikely to result from an epileptic mechanism, as an adverse effect of breathing hyperoxic mixtures.

A rare case of intracranial malignant triton tumor arising in the middle cranial fossa: a case report and review of the literature.

We describe a rare case of intracranial malignant triton tumor (MTT) arising in the middle cranial fossa in a 74-year-old female patient who had previously been exposed to radiation in the Chernobyl disaster. The patient underwent a surgical subtotal removal of the mass and radiation therapy, but the progression-free survival was only 2.5 months and death occurred four months after the onset of symptoms. MTTs are rare aggressive tumors arising from the nerve sheath showing rhabdomyosarcomatous differentiation and associated with a poor prognosis. The intracranial location is very rare, and only 10 cases, including the present report, have been described so far. Among intracranial MTTs, the cerebellopontine angle is the most common location. Neurofibromatosis type 1 (NF-1) and radiation exposure are risk factors as for MTTs located in other sites. The gold standard therapy is surgical excision followed by radiation therapy, but the prognosis is usually very poor.

Using STN DBS and medication reduction as a strategy to treat pathological gambling in Parkinson's disease.

We describe two patients with Parkinson's disease (PD) who developed clinical criteria of pathological gambling addiction in the setting of increased dopamine replacement therapy (levodopa and dopamine agonist medications). The second patient showed also signs of dopamine dysregulation syndrome, with an addiction to dopaminergic medication. Neither patients responded to the standard therapy for gambling behavior, but dramatically improved after bilateral subthalamic nucleus (STN) deep brain stimulation (DBS) and early postoperative withdrawal of dopaminergic therapy. The possible therapeutic role of subthalamic nucleus deep brain stimulation (STN-DBS) on such a disabling behavior needs to be investigated prospectively.

Prevalence and cognitive underpinnings of isolated apathy in young healthy subjects.

BACKGROUND: Apathy is well described in neurodegenerative conditions, however to date there is no evidence of significant isolated apathy in subjects free from other neurological and psychiatric co-morbidites. Identifying isolated apathy in subjects free from neuropsychiatric conditions could contribute to refining current concepts of apathy and reevaluate its nosological classification as an independent clinical syndrome. METHODS: We assessed apathy and perceived quality of life in a group of 2751 adults (age 19-40 years) free from neuropsychiatric or medical conditions. Subjects with and without elevated apathy were compared on measures of depression, self-efficacy, behavioral inhibition, and behavioral activation. RESULTS: Observed prevalence of isolated elevated apathy was 1.45%. Subjects with apathy presented with reduced quality of life and lower behavioral activation compared to apathy-free subjects, while there was no difference between the two groups on measures of depression, self-efficacy, and perceived social skills. LIMITATIONS: The main limitation of this study is the use of self-report questionnaires. CONCLUSIONS: Isolated, ecologically-relevant apathy can be found in adults independently from the presence of subclinical depression or of concurrent medical conditions. Apathy screening should be considered in the evaluation of young non-depressed subjects with reduced perceived quality of life.

Cognitive recovery after delayed carbon monoxide encephalopathy.

We report on a patient with delayed carbon monoxide encephalopathy who presented with severe cognitive impairment associated with MRI findings of extensive demyelination of the cerebral white matter after a silent period of three weeks from acute intoxication. Despite the severe signs of structural and functional cerebral impairment in the sub-acute stage, the clinical course was favorable but for residual mild dysfunction of the frontal lobes.

Progressive multifocal leukoencephalopathy in an adult patient with ICF syndrome.

We report on a patient affected by ICF syndrome (immunodeficiency, centromeric instability of chromosomes 1, 9 and 16 and facial dysmorphism), who presented with slowing in mentation, mild right hemiparesis and focal motor seizures. MRI study of the brain suggested a diagnosis of progressive multifocal leukoencephalopathy (PML), which was confirmed by JC virus DNA detection on CSF by polymerase chain reaction (PCR). This is a unique case of adult infective neurological complication described in ICF Syndrome.

Ifosfamide encephalopathy and nonconvulsive status epilepticus.

BACKGROUND: Ifosfamide (IFX), an alkylating agent and isomer of cyclophosphamide, is used as a single agent or a component of multi-agent chemotherapy in the treatment of ovarian, testicular, head and neck cancers, sarcomas and lymphomas. Encephalopathy is manifested by cerebellar ataxia, confusional state, complex visual hallucinations, extrapyramidal signs, seizures, and mutism. CASE REPORTS: We report two patients with non-Hodgkin's lymphoma presenting with mutism and confusional state after IFX infusion. Nonconvulsive status epilepticus (NCSE) as the cause of confusion was diagnosed on the basis of EEG pattern and the apparent improvement following intravenous administration of diazepam. CONCLUSIONS: Electroencephalogram abnormalities during IFX treatment have been described but recordings are only available in six cases. In three of them, paroxysmal alterations warranted the diagnosis of NCSE; however, most cases of IFX encephalopathy might have associated NCSE.

Diffusion magnetic resonance imaging diagnostic relevance in pyogenic ventriculitis with an atypical presentation: a case report.

BACKGROUND: Pyogenic ventriculitis is a rare and severe cerebral infection characterized by the presence of suppurative fluid in the cerebral ventricles. It is a life-threatening condition and may present with an aspecific neurological picture. Brain imaging techniques usually demonstrate intraventricular debris and pus, but negative imaging along with a misleading clinical picture may delay the diagnosis. CASE PRESENTATION: The described patient underwent a number of surgical procedures and eventually developed an unusual clinical picture characterized by psychomotor slowing, facial dyskinesias and myoclonic jerks without complaint of headache and in absence of meningeal irritation signs or focal neurological deficits. Cerebrospinal fluid cultural examination showed methicillin-resistant Staphylococcus aureus and vancomycin treatment lead to a complete recovery. Brain computed tomography scan was normal, while only diffusion magnetic resonance imaging sequences were able to define the presence of purulent material within the brain lateral ventriculi. CONCLUSION: The present case underlines the importance of taking into account the diagnosis of pyogenic ventriculitis even when the neurological picture does not match the suspect of a central nervous system infection. Moreover, brain computed tomography scan and standard magnetic resonance imaging sequences may be unable to confirm the diagnosis, whereas diffusion-weighted sequences prove a unique role in diagnosing cerebral pyogenic ventriculitis.

Altered handwriting suggests cognitive impairment and may be relevant to posthumous evaluation.

Judging the validity of a disputed will is complex; however, one of the main issues is what the mental status of the testator was at the time of the will. If the will is handwritten, a handwriting analysis can provide information on the mental status of the testator. We tested how two writing parameters (the "writing score," a novel evaluation scale that we previously described, and the percentage of spelling mistakes) are capable to identify cognitively impaired persons. These parameters are especially helpful because they can be used to evaluate the mental status of a deceased person. We found a significant correlation between either parameter and established scales of neuropsychological evaluation (Mini Mental State Examination and Milan Overall Dementia Assessment scale). Specifically, a poor score on either parameter reliably identified a compromised cognitive status. These may represent helpful additions to existing techniques in posthumously identifying persons with severe cognitive impairment.

Amisulpride vs. fluoxetine treatment of chronic fatigue syndrome: a pilot study.

Different pharmacologic agents have been evaluated in the treatment of Chronic Fatigue Syndrome (CFS), albeit with moderate efficacy. Among the compounds thought to present with potential to be efficacious in CFS patients stands out low-dose amisulpride, a substituted benzamide that has been shown to be an useful treatment for conditions which exhibit some overlap with CFS such as dysthymia and somatoform disorders. We thus recruited forty non-depressed CFS patients that were randomized to receive either amisulpride 25mg bid, or fluoxetine 20mg uid; all subjects were un-blinded to the treatment regimen. At the time of enrollment in the study and after twelve weeks of treatment, enrolled subjects completed the Krupp Fatigue Severity Scale, the Hospital Anxiety and Depression Scale and a visual analog scale focused on pain and bodily discomfort. Moreover, all subjects were evaluated by a clinician, blinded to the treatment regimen, using the Clinical Global Impression Severity Scale. Our data revealed a significant improvement both in self-report, and observer-based measures for the amisulpride-treated, but not for the fluoxetine-treated patients. Amisulpride-treated subjects also presented with a significant reduction of somatic complaints, while the amisulpride effect on anxiety and mood levels was not significant. Both drugs were equally well tolerated. Summing up, we showed a positive symptomatic effect of amisulpride, compared to SSRI treatment, in a group of non-depressed CSF patients on self-report and on observer-based measures of fatigue and somatic complaints. If confirmed by larger, blinded studies, amisulpride thus could represent an effective approach to this difficult-to-treat condition.

Handwriting as a gauge of cognitive status: a novel forensic tool for posthumous evaluation of testamentary capacity.

OBJECTIVE: To provide an objective way to analyze handwriting, and to test its reliability and correlation with mental deterioration. Handwriting may give clues to the cognitive status of the writer, thus its analysis might be helpful, for example, in the forensic evaluation of a controversial handwritten last will. DESIGN: We devised a semiquantitative score system taking into account verbal and lexical skills and spatial orientation. We investigated its inter-rater reliability and its correlation with validated tests of neuropsychological status, such the Milan Overall Dementia Assessment (MODA) and the Mini Mental State Examination (MMSE). SETTING: The neuropsychology service of an academic hospital. PATIENTS AND PARTICIPANTS: Consecutive patients referred to the service for evaluation of mental deterioration. MEASUREMENTS AND RESULTS: The score system we devised has good inter-rater reliability and significantly correlates with MODA and with MMSE. CONCLUSIONS: Semiquantitative analysis of handwriting may be a useful addition to the methods available for the posthumous evaluation of testamentary capacity.

Nonconvulsive status epilepticus during cephalosporin therapy.

Cephalosporins may induce nonconvulsive status epilepticus (NCSE), a potentially reversible condition. Despite the wide use of these antibiotics, there are only few reported cases, because this condition is probably underestimated. We report two new cases of NCSE occurring during treatment with cefepime and ceftazidime, and emphasize the utility of emergent electroencephalogram in patients with an acute altered state of consciousness while receiving treatment with cephalosporins, particularly when there is evidence of impaired renal function.