Neuropsychological evaluation of late-onset post-radiotherapy encephalopathy: a comparison with vascular dementia.

It is known that radiotherapy (RT) may cause cerebral injury. The most frequent neurotoxic effect of RT at any age is diffuse cerebral injury. Brain injury by therapeutic irradiation has traditionally been classified according to its time of onset into acute, early delayed, and late forms. The latter is not reversible. The neurocognitive sequelae of cranial irradiation can be mediated through vascular injury. Because the pathologic changes are most profound in the white matter, we compared a group of patients treated by RT (n=34) with a group of patients affected by subcortical vascular dementia (sVaD, n=34). Patients with a total radiation does <35 cGy did not show any sign of cognitive impairment. All the patients with a total irradiation dose >45 cGy did show profound cognitive and behavioural alteration. The patients who received a total dose of brain radiation comprised between 35 and 45 cGy did show slowness of executive function, and profound alterations of frontal functions, such as attention focusing, mentation control, analogical judgement and insight. The patients who suffered from the consequences of RT had slowness of executive functions, and profound alterations of frontal functions, such as attention focusing, mentation control, analogical judgement and insight, similar to those obtained by the patients suffering from subcortical vascular dementia. High dose RT might result in a severely demented, bedridden patient, who "has been cured" from his primary disease, the brain tumour. This constellation demands serious consideration before RT is given.

Use of the ten-point clock test to compare executive functioning across 24 months in patients with subcortical vascular dementia.

The Ten-point Clock Test can be used to identify early forms of Alzheimer's disease because it is reliable, well accepted, and easily administered at the bedside. Nevertheless, its clinical role in the detection of early dementia and its correlations with other cognitive processes is still under investigation. Vascular dementia is an uncertain nosological entity, in which unevenly distributed patterns of cognitive deficits comprising slowing of cognitive processing and impairment of executive function occur. The present study assessed how the Clock Test scores correlated with a number of other neuropsychological and functional tests in a sample of 144 patients with vascular dementia, who were followed for a period of 24 mo. At baseline, at 12 mo. and at 24 mo. subjects were administered a battery of tests, including the Mini-Mental State Examination, word fluency, visuospatial skills, an evaluation of hetero- and autotopognosia (knowledge of self), the Proverbs Test, and the Ten-point Clock Test. For these patients scores on the Clock Test correlated significantly with semantic abilities, with abstract reasoning capacities, visuospatial perception, and with right and left recognition.

Frontal lobe dementia and subcortical vascular dementia: a neuropsychological comparison.

We compared the performance of 40 patients with frontal lobe dementia to that of 40 patients with subcortical vascular dementia (80 patients including, 46 men and 34 women) in a set of tasks assessing attentional, executive, and behavioural tasks. The frontal lobe dementia represents an important cause for degenerative disruption and is increasingly recognised as an important form (up to 25%) of degenerative dementia among individuals of late-middle-age. The main involvement is the frontal-subcortical pathway, which is the final target of impairment even in subcortical vascular dementia. A wider involvement of the cortical (decisional) layers in frontal dementia, in contrast with the prominent and widespread involvement of the subcortical pathways (refinement and corrections programs) creates the different profiles of the two groups. Frontal patients have more difficulties in abstract reasoning, focusing attention, and implementing strategies to solve problems. They exhibit more profound behavioural alterations in personality and social conduct and show only moderate depression, and a total lack of insight concerning their dinical condition. In contrast, the patients with subcortical vascular dementia have poor general cognitive functions, high insight, and important depression and apathy as the principal and most salient characteristic of their behavioral conduct.

Language recovery following subthalamic nucleus stimulation in Parkinson's disease.

Neuropsychological consequences of stimulation of the subthalamic nucleus for treatment of drug-resistant Parkinson's disease (PD) have been studied previously. However, no detailed investigations of linguistic function modifications have been carried out. We studied four consecutive patients with PD who underwent chronic bilateral stimulation of the subthalamic nuclei. Neuropsychological and linguistic evaluations were performed before and 2 weeks after surgery. Linguistic abilities were studied also 1 year after surgery with stimulators both off and on. Intraphrasal hesitation pauses, phonemic paraphasias and morpho-syntactic errors were significantly reduced and lexical retrieval improved with stimulation of the subthalamic nuclei. Implicit linguistic phenomena, mainly occurring within basal ganglia circuitry, benefited by recovery of functional equilibrium within basal nuclei and between overall basal ganglia circuitry and cerebral cortex.

Reading errors in patients with cerebellar vermis lesions.

Dyslexia, both developmental and acquired, has been considered the result of cerebrocortical dysfunction, affecting the temporo-parieto-occipital brain regions. However, dyslexia may involve abnormalities of the magnocellular component of the visual system, leading to binocular instability or alterations of accommodation. To test the hypothesis of cerebellar involvement in the reading process -- justified by its emergent role in language and cognition -- we studied 10 patients with cerebellar vermis/paravermis lesions using reading tests and we compared the results with those produced by 10 normal volunteers. The data obtained demonstrate an increased number of reading mistakes in the patient group, resulting from a possible alteration of the diffuse connection system from the cerebellum to different cerebrocortical and subcortical structures. Acquired dyslexia due to cerebellar impairment may be due to oculomotor alteration or, more subtly, to the intimate cerebellar-encephalic projections, connecting the cerebellum to the attentive and alerting processes and to the language system. We discuss the data with an overview of literature.

Gabapentin treatment of glossopharyngeal neuralgia: a follow-up of four years of a single case.

Glossopharyngeal neuralgia causes intermittent, lancinanting pain, involving the posterior tongue and pharynx, with radiation to deep ear structures. There are different pharmacological therapies which are tried to treat the neuralgia: carbamazepin, phenytoin, diazepam, amytriptyline, phenobarbital, ketamine, and baclofen; there are also surgical treatment proposed in order to cure the neuralgia such as vascular decompression or electrical stimulation of the motor cortex controlateral to the pain area. We report a single case of a patient with glossopharyngeal neuralgia treated with Gabapentin, the first described, who was followed up for four years, who respond completely to the therapy and did not complain from side effects, reducing even the reminiscence of pain during the second cluster of crisis.

Rivastigmine in subcortical vascular dementia: an open 22-month study.

Further to recent data indicating that patients with vascular dementia (VaD) show a cholinergic deficit, we aimed to determine whether rivastigmine, a dual inhibitor of acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE), has any effects on the symptoms of VaD. Patients aged 65-80, with a diagnosis of dementia and probable VaD, received rivastigmine 3-6 mg/day (n=8) or cardioaspirin (n=8) in an open study for 22 months. At 22 months, patients treated with rivastigmine showed significant improvements in executive function and behavioural symptoms (both p<0.05 vs. both baseline and control group), which were reflected in reduced caregiver stress (p<0.05 vs. baseline and controls). Baseline scores of global response, cognition, word fluency and activities of daily living were maintained in patients receiving rivastigmine, and there was no increase in benzodiazepine or neuroleptic intake. In contrast, the control group showed no improvements in any domain, and significant deterioration in global response and executive function (both p<0.05 vs. baseline and rivastigmine group). Side effects in both groups were tolerable and there were no study withdrawals. Long-term rivastigmine treatment appeared to be safe and effective in this patient population. In particular, improvements in domains particularly relevant to this condition were observed. These benefits may reflect the drug's dual inhibitory effects on the cholinergic system, and its particular activity in frontal areas of the brain. A large, double-blind study of rivastigmine in patients with VaD would be worthwhile.

Gabapentin as a drug therapy of intractable hiccup because of vascular lesion: a three-year follow up.

BACKGROUND: Persistent and intractable hiccups indicate multiple neurologic and extraneurologic disorders. Chronic hiccup is not so rare in patients suffering from stroke: its impact on quality of life and on rehabilitation management is substantial, and it may be closely related to aspiration pneumonia, respiratory arrest and nutritional depletion. REVIEW SUMMARY: Intractable hiccups can be associated with potentially fatal consequences and safe management may require inpatient rehabilitation. It has been suggested that hiccups could be a form of myoclonus, caused by repeated and abnormal activity of the solitary inspiratory nucleus. Because of this cause we decided to treat intractable hiccups in patients with ischemic lesions of the medulla with a short course of gabapentin. CONCLUSIONS: The results were promising, with the immediate disappearance of the hiccups, and the complete absence of side effects. The 36-months follow up was favorable to all the patients, who, after 6 days of treatment remain asymptomatic.

Gabapentin for the treatment of behavioural alterations in dementia: preliminary 15-month investigation.

BACKGROUND: Although the core feature of dementia is progressive cognitive disruption, non-cognitive behavioural problems are expressed in most patients with dementia during the course of their illness. While psychotropic drugs are frequently used to control behavioural symptoms, comorbidities, which are very common in the geriatric population, could often limit their use. Gabapentin may be a potential treatment in such situations. METHODS: In this open, baseline comparison study 20 patients with probable Alzheimer's disease with behavioural alterations and serious comorbidities (paralytic ileus, open-angle glaucoma, ischaemic cardiopathy, hepatic failure or severe prostatic hyperplasia) received gabapentin for 15 months. Patients were allowed to continue any previous therapy for concurrent diseases. However, concomitant antipsychotic or benzodiazepine intake was not permitted. RESULTS: Gabapentin appeared to be efficacious and well tolerated in this patient population, and did not appear to interact with other drugs. General benefit is reflected by a reduction of caregiver stress. No patients withdrew before the end of the study and no serious adverse events were reported. CONCLUSION: The results of this study in patients with probable Alzheimer's disease with behavioural alterations and serious comorbidities indicate that gabapentin provides significant and sustained efficacy in terms of behaviour, with associated reductions in caregiver burden. The results of an ongoing larger, randomised, double-blind study of gabapentin are keenly awaited and may help to provide a safer and more efficacious treatment option for this group of patients.

Rivastigmine in frontotemporal dementia: an open-label study.

OBJECTIVE: This preliminary open-label study aims to investigate the effects of rivastigmine, an inhibitor of acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE), in 20 patients diagnosed with frontotemporal dementia (FTD). PATIENTS AND METHODS: Study subjects were men and women 60-75 years of age diagnosed with probable FTD. The rivastigmine group received doses of 3-9 mg/day. The control group included matched patients receiving antipsychotics, benzodiazepines and selegiline (deprenyl). All patients completed a 12-month follow-up period. RESULTS: Rivastigmine treatment was well tolerated. At 12 months, there was a general amelioration of behavioural changes as demonstrated by reductions in Neuropsychiatric Inventory (p<0.001 vs baseline and control), Behavioral Pathology in Alzheimer's Disease Rating Scale (p<0.001 vs baseline and control) and Cornell Scale for Depression in Dementia scores (p<0.05 vs baseline, p<0.001 vs control) in the rivastigmine group. Caregiver burden was reduced, as shown by reduced Relative Stress Scale scores (p<0.001 vs baseline and control). Mean scores on outcome measures evaluating executive function stabilised in the rivastigmine group (p<0.05 vs controls). Rivastigmine did not prevent the disease-related deterioration of cognition as assessed using the Mini-Mental State Examination. CONCLUSION: In this open-label study, rivastigmine-treated patients were less behaviourally impaired, and caregiver burden was reduced, at 12 months, compared with baseline. The use of cholinesterase inhibitors in FTD warrants further research.

Neuropsychological changes after subthalamic nucleus stimulation: a 12 month follow-up in nine patients with Parkinson's disease.

Deep brain stimulation of the subthalamic nucleus has been recognized as one of the most promising techniques to decrease 'off' motor symptoms and motor fluctuations, allowing a reduction of drug therapy and limiting side effects of drug therapy. However, there is still open debate on the possible consequences of chronic subthalamic stimulation on general cognitive performance. A general amelioration of cognitive performance, in particular of executive functions has been reported but results are not homogeneous. We studied nine patients with Parkinson's Disease for 12 months following surgery for deep stimulation, studying their cognitive performances, paying particular attention to linguistic tests and selective alternating words production. Our results may be consistent with a slowing of cognitive activity, with a reduction of quantitative production, but with an increase in control of linguistic production, which is more precise and definite. We discuss the possible significance of these results, fully aware that only nine patients were involved, and that the potential for generalization is seriously limited, with a particular overview on the frontal-subthalamic pathway, which in our opinion is responsible for the results we observed.

Rivastigmine in vascular dementia.

Patients with vascular dementia (VaD) show cholinergic deficits that may result in characteristic clinical syndromes for different subtypes of the condition. Subcortical VaD is characterised by executive dysfunction and behavioural problems, reflecting deterioration of the frontal lobe. Based on limited open-labelled controlled studies of rivastigmine in VaD, this article aims to determine whether rivastigmine, a dual inhibitor of acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE), has any effects on the typical symptoms of subcortical VaD. Long-term rivastigmine treatment is safe and effective. Improvements in domains that characterise subcortical VaD were observed, indicating that rivastigmine may have provided targeted treatment in areas of the brain that are particularly affected in this patient population. A large, double-blind study of rivastigmine in patients with VaD is clearly warranted.

Depression and Alzheimer's disease: symptom or comorbidity?

Alzheimer's disease is the most frequent form of dementia, where behavioral and cognitive disruption symptoms coexist. Depression, apathy, anxiety, and other conduct disorders are the complaints most often reported by caregivers. Fifty subjects were referred to our Institute with a diagnosis of probable Alzheimer's disease. Cognitive impairment was equally distributed among the subjects. Patients, aged 68 to 76 years old, were randomized to receive inhibitors of cholinesterase (Donepezil, 5 mg/day) alone, or inhibitors of cholinesterase plus selective serotonin reuptake inhibitors (SSRIs) (citalopram HBr, 20 mg/day). We followed up all the patients for one year, with particular concern for neuropsychological aspects associated with eventual behavioral changes. Results indicate that SSRI intake seems to be effective for depression, decreasing it and improving quality of life for both patients and caregivers. Side effects in both groups were few, and there were no study withdrawals. This paper discusses the relationship between dementia and depression, and presents our finding that depressive symptoms, if specifically treated, tend to reduce caregiver stress and improve well-being in patients with Alzheimer's disease.

Rivastigmine in subcortical vascular dementia: a randomized, controlled, open 12-month study in 208 patients.

Subcortical vascular dementia (VaD) is characterized by executive dysfunction and behavioral problems, reflecting deterioration of the frontal lobe. This study aimed to determine whether rivastigmine, a dual inhibitor of acetylcholinesterase (AChE) and butyryl-cholinesterase (BuChE), has any effects on the typical symptoms of subcortical VaD. Patients receiving rivastigmine showed a slight improvement in executive functions and in behavior. Side effects in both groups were tolerable and there were no study withdrawals. Moreover, there are no drug interactions with other therapies previously and concomitantly assumed. Improvements in domains that characterize subcortical VaD were observed, indicating that rivastigmine may have provided targeted treatment in areas of the brain that are particularly affected in this patient population.

Olanzapine as a possible treatment for anxiety due to vascular dementia: an open study.

Disabilities caused by behavioral problems can be potentially devastating in cognitively impaired patients. These behavioral symptoms can be a major cause of stress, anxiety, and concern for caregivers. While psychotropic drugs are frequently used to control these symptoms, they can be accompanied by significant side effects, which include sedation, disinhibition, depression, falls, incontinence, parkinsonism, and akathisias. Agitation is a major problem in older patients with dementia. Agitation and aggression have always been difficult behaviors to manage, and when it is severe, agitation can be a behavioral emergency that requires urgent and immediate intervention. This six-month study included a group of 94 outpatients (48 men and 46 women) who had a diagnosis of subcortical vascular dementia (VaD). To be eligible for the study, patients needed a score of at least 3 for agitation/aggression on the Neuropsychiatric Inventory (NPI), suggesting at least moderate frequency and/or severity, and 0 for delusions and hallucinations. Patients were divided into two homogenous groups. Group A received olanzapine (2.5-5 mg/day) and Group B received bromazepam (0.25 percent, 15 drops, three times per day). Patients in both groups were allowed to continue any previous therapy. Patients receiving olanzapine at an average dose of 3.21 +/- 1.02 mg/day showed statistically significant improvement on the anxiety rating compared with those receiving bromazepam. Our patients had a host of medical conditions and received numerous concomitant medications. Given the potential complications associated with these therapeutic agents, these patients tolerated olanzapine quite well. It appeared that adverse events, particularly somnolence, postural instability, and postural hypotension, were mild and transient. Moreover, no anticholinerigic effect was registered. These findings suggest that olanzapine could be a safe and effective treatment for anxiety in cognitively impaired patients.

Olanzapine as a treatment of neuropsychiatric disorders of Alzheimer's disease and other dementias: a 24-month follow-up of 68 patients.

Although the core feature of all types of dementia is progressive cognitive disruption, most demented patients also express noncognitive behavioral problems. These noncognitive problems lead to potentially devastating disabilities, and are often a major cause of stress, anxiety and concern for caregivers. Psychotropic drugs are frequently used to control these symptoms, but they have the potential for significant side effects, such as sedation, disinhibition, depression, falls, incontinence, parkinsonisms and akathisias. For 24 months, we monitored 68 outpatients suffering from Alzheimer's disease, vascular dementia, frontal lobe dementia, Parkinson dementia complex, and Lewy body disease. Our purpose was to identify the role and efficacy of olanzapine and the side effects which emerged during the treatment of behavioral alteration resulting from five etiological causes. This paper will discuss the results of this study, and will provide an overview of the existing literature.

Complex distal movement in cortical-basal ganglionic degeneration. A functional evaluation.

We evaluated cortical activation during simple and complex learned movements in five patients diagnosed with cortical-basal ganglionic degeneration. Since the parietal area is one of the areas most involved in this degenerative pathology, we focused on the possible role of the parietal lobe, in learning and executing simple and complex motor sequences. We also attempted to describe the role of the parietal area in spatial and visual control, which is necessary to define and optimise movement execution in daily living. We discuss the results of our evaluation, and give an overview of the literature on the topic.

Vitamin B12 and folate depletion in cognition: a review.

In cross-sectional studies, low levels of folate and B12 have been shown to be associated with cognitive decline and dementia Evidence for the putative role of folate, vitamin B12 in neurocognitive and other neurological functions comes from reported cases of severe vitamin deficiencies, particularly pernicious anemia, and homozygous defects in genes that encode for enzymes of one-carbon metabolism. The neurological alterations seen in these cases allow for a biological role of vitamins in neurophysiology. Results are quite controversial and there is an open debate in literature, considering that the potential and differential role of folate and B12 vitamin in memory acquisition and cognitive development is not completely understood or accepted. What is not clear is the fact that vitamin B12 and folate deficiency deteriorate a pre-existing not overt pathological situation or can be dangerous even in normal subjects. Even more intriguing is the interaction between B12 and folate, and their role in developing hyperhomocysteinemia. The approach to the rehabilitation of the deficiency with adequate vitamin supplementation is very confusing. Some authors suggest it, even in chronic situations, others deny any possible role. Starting from these quite confusing perspectives, the aim of this review is to report and categorize the data obtained from the literature. Despite the plausible biochemical mechanism, further studies, based on clinical, neuropsychological, laboratory and (lastly) pathological features will be necessary to better understand this fascinating biochemical riddle.

Writing errors by normal subjects.

Writing is a complex process requiring visual memory, attention, phonological and semantic operations, and motor performance. For that reason, it can easily be disturbed by interfering with attention, memory, by interfering subvocalization, and so on. With 16 female third-year students (23.4 +/- 0.8 yr.) from the University of Trieste, we investigated the production of errors in three experimental conditions (control, articulatory suppression, and tapping). In the articulatory suppression condition, the participants produced significantly more linguistic impairments (such as agrammatism, unrelated substitutions, sentence omissions, and semantically deviant sentences), which are similar to linguistic impairments found in aphasia. On the tapping condition there were more perseverations, deletions, and substitutions of both letters and words. These data suggest that writing is not an automatic skill. Only after many years of experience and practice of processing information (through cortical to subcortical channels) can writing be considered an automatic skill. Limited experimental conditions can disrupt the writing system of normal subjects, probably interfering with the cortical to subcortical loops, and link normality to pathology.

Cognitive changes following subthalamic nucleus stimulation in two patients with Parkinson disease.

The limits of a drug therapy in severe forms of Parkinson disease have led to refining neurosurgery on the basal ganglia. Deep brain stimulation of the subthalamic nucleus has been recognized as one of the most promising techniques to decrease "off" motor symptoms and motor fluctuations, allowing a reduction of drug therapy and limiting side effects of the drugs. There is still open debate on the possible consequences of chronic subthalamic stimulation in other ways, apart from motor symptoms, of general cognitive performance. We examined and followed two patients with Parkinson disease for 9 mo. after surgery for deep stimulation, studying their cognitive performances. There is a general amelioration of cognitive performances, in particular as far as linguistic capabilities is concerned. We discuss the possible significance of these results, reminding strenuously that only two patients were involved, so the potential for generalization is seriously limited.